er-086526 and Neoplasm-Metastasis

Eribulin therapy has been reported to prolong overall survival (OS) but not progression-free survival, probably because it prevents the development of metastatic lesions; however, this effect has not yet been confirmed.. We reviewed the medical charts of 50 patients with metastatic breast cancer who underwent eribulin monotherapy at our hospital between 2014 and 2019. Patients were divided into two groups, namely, those who discontinued eribulin because of disease progression due to development of new lesions (NL group) and those who discontinued eribulin for other reasons, such as lesion growth and unacceptable side effects (non-NL group). Survival times were estimated for both groups and we investigated if eribulin-mediated suppression of new metastasis increased OS.. Median OS for all patients, from eribulin initiation, was 14.4 months (range 1.2-60.1), whereas it was 4.6 months (range 1.7-24.7) in the NL group and 16.8 months (range 1.2-60.1) in the non-NL group. OS was significantly poorer in the NL group than in the non-NL group (p < 0.05).. Eribulin monotherapy-mediated suppression of new metastatic lesions results in a better prognosis in patients with metastatic breast cancer.

Topics: Antineoplastic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Neoplasm Metastasis; Prognosis; Treatment Outcome

Eribulin mesylate (ERI; Halaven®) is a microtubule inhibitor approved in the United States for metastatic breast cancer patients with at least two prior chemotherapy regimens for metastatic breast cancer, and in the European Union in locally advanced breast cancer or metastatic breast cancer patients who progressed after at least one chemotherapy for advanced disease. This network meta-analysis compared the efficacy and safety of ERI versus other chemotherapies in this setting.. Systematic searches conducted in MEDLINE, Embase, and the Cochrane Central Register of Clinical Trials identified randomized controlled trials of locally advanced breast cancer/metastatic breast cancer chemotherapies in second- or later-line settings. Efficacy assessment included pre-specified subgroup analysis of breast cancer subtypes. Included studies were assessed for quality using the Centre for Reviews and Dissemination tool. Bayesian network meta-analysis estimated primary outcomes of overall survival and progression-free survival using fixed-effect models. Comparators included: capecitabine (CAP), gemcitabine (GEM), ixabepilone (IXA), utidelone (UTI), treatment by physician's choice (TPC), and vinorelbine (VIN).. The network meta-analysis included seven trials. Results showed that second- or later-line patients treated with ERI had statistically longer overall survival versus TPC (hazard ratio [HR]: 0.81; credible interval [CrI]: 0.66-0.99) or GEM+VIN (0.62; 0.42-0.90) and statistically longer progression-free survival versus TPC (0.76; 0.64-0.90), but statistically shorter progression-free survival versus CAP+IXA (1.40; 1.17-1.67) and CAP+UTI (1.61; 1.23-2.12). In triple negative breast cancer, ERI had statistically longer overall survival versus CAP (0.70; 0.54-0.90); no statistical differences in progression-free survival were observed in triple negative breast cancer.. This network meta-analysis suggests that ERI may provide an overall survival benefit in the overall locally advanced breast cancer/metastatic breast cancer populations and triple negative breast cancer subgroup compared to standard treatments. These findings support the use of ERI in second- or later-line treatment of patients with locally advanced breast cancer/metastatic breast cancer.

Topics: Breast Neoplasms; Female; Furans; Humans; Ketones; Neoplasm Metastasis; Network Meta-Analysis; Progression-Free Survival

Eribulin is a novel microtubule inhibitor with mitotic and nonmitotic mechanisms of action. Both pooled and subgroup analyses from large-scale Phase III clinical trials demonstrated that eribulin has substantial activity in patients with pretreated (anthracycline and a taxane) advanced or metastatic breast cancer. We review recent pharmacological and clinical findings pertaining to eribulin use in metastatic breast cancer - particularly highlighting eribulin in difficult-to-treat and aggressive disease, and safety data in specific patient populations. Additionally, recent advancements in our understanding of the mechanism of action of eribulin and potential future directions for its clinical development are discussed. Ongoing studies of eribulin in combination with immunotherapies and established cytotoxic agents may help shape the future landscape of breast cancer treatment.

Topics: Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Clinical Trials as Topic; Female; Furans; Genes, erbB-2; Humans; Ketones; Neoplasm Metastasis; Neoplasm Staging; Treatment Outcome; Tubulin Modulators

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Furans; Humans; Ketones; Neoplasm Metastasis; Survival Rate

Metastatic soft tissue sarcoma, a devastating disease, has a median overall survival of only 12-18 months. Treatment options remain scarce. However, eribulin mesylate, a first-in-class halichondrin B-based microtubule dynamics inhibitor, has recently been approved for the management of patients with advanced liposarcoma. Areas covered: Based on a review of the literature between 2005 and 2017, we present a summary of eribulin mesylate's mechanism of action and the studies showing its clinical efficacy in locally advanced or metastatic sarcomas. Expert commentary: Future development includes the definition of a biomarker signature related to patient outcome with eribulin. Further investigation via controlled clinical trials is needed to identify combination regimens that can optimize the efficacy of eribulin while providing an acceptable safety profile in sarcoma patients.

Topics: Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Disease-Free Survival; Epithelial-Mesenchymal Transition; Ethers, Cyclic; Female; Furans; Humans; Ketones; Macrolides; Neoplasm Metastasis; Sarcoma; Tubulin Modulators

Eribulin is a synthetic analog of halichondrin B belonging to microtubule-targeted agents with a distinct mechanism of inhibition of microtubule dynamics. This molecule has multiple nonmitotic effects on tumor biology, exhibiting effects on epithelial-mesenchimal transition and tumor vasculature. We review here preclinical and clinical studies on eribulin. The mitotic and nonmitotic effects together with its favorable safety profile make eribulin a unique drug with high potential in the treatment of metastatic breast cancer. The new emphasis of eribulin mechanism of action on vascular remodeling, microenvironment modifications and reversal of epithelial-mesenchimal transition paves the way to rethinking the use of the drug in an immunological perspective.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Evaluation, Preclinical; Female; Furans; Humans; Ketones; Microtubules; Neoplasm Metastasis; Neoplasm Staging; Treatment Outcome

Eribulin is one of the newer chemotherapeutic agents approved for use in later line treatment of patients with metastatic breast cancer. Phase III studies have shown a useful clinical response rate for eribulin as well as equivalence to another commonly used drug in metastatic breast cancer, capecitabine. Nevertheless, whether this clinical value observed in trial patients is maintained in patients seen in clinical oncology practice, outside trials remains a question. Several series published over the last few years sought to answer this question. The current paper carries out a pooled analysis of these retrospective series to obtain efficacy and toxicity data for eribulin in metastatic breast cancer patients treated off trials. Thirteen series with a total of 1095 patients were identified. Pooled estimates of response rate and clinical benefit rate were 20.1% (95% confidence interval: 16.3-23.9%) and 46.3% (95% confidence interval: 39.4-53.2%) respectively. These were somewhat higher than the response rate and clinical benefit rate observed in a pooled analysis of two randomized phase III trials (14.9 and 30.9%, respectively, conducted in an intension-to-treat manner). In contrast overall survival was longer in the phase III trials (median 15.2 months) than in the retrospective studies (pooled estimate 9.8 months). All grades toxicities were similar in practice compared with trials with slightly higher grade 3 toxicities (46.1 vs. 38.7%) but lower grade 4 toxicities (17.2 vs. 27.7%) in patients off trials.

Topics: Antineoplastic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Neoplasm Metastasis; Retrospective Studies

Breast cancer is the second leading cause of cancer death among women and the median survival of metastatic breast cancer (MBC) has remained, for many decades, at two to three years after diagnosis. Eribulin mesylate is a nontaxane inhibitor of microtubule dynamics and the only cytotoxic agent in the last decade to improve overall survival in heavily pretreated patients with MBC. Eribulin was approved for the treatment of MBC in 2010 by the FDA in patients that received at least two prior chemotherapy regimens and as second-line treatment in 2011 by EMA. In both cases prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.. This manuscript reviews the current available data on the use of this important cytotoxic agent including its pharmacology, pharmacokinetics, clinical efficacy, safety, and potential economic factors as well as ongoing clinical trials and main areas of research.. Eribulin mesylate is a novel microtubule dynamics inhibitor compound important for the management of MBC and can be used for the treatment of patients who have previously received one/two chemotherapeutic regimens for metastatic disease and whose prior therapy included an anthracycline and a taxane. It's toxicity profile is acceptable and presents several favorable features namely a low probability of drug-drug interactions in the clinical setting, easy administration as bolus, low hypersensitivity chances and full tolerability in renal dysfunction patients. Eribulin is currently being evaluated as first-line treatment for MBC, in the adjuvant/neoadjuvant setting alone and in combination with a variety of agents, particularly biologic treatments. Future research is needed to optimize the role of eribulin in the treatment of MBC.

Topics: Antineoplastic Agents; Breast Neoplasms; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Resistance, Neoplasm; Female; Furans; Humans; Ketones; Neoadjuvant Therapy; Neoplasm Metastasis; Tubulin Modulators

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of eribulin (Eisai Ltd) to submit evidence for the clinical and cost effectiveness of eribulin as treatment for patients with locally advanced or metastatic breast cancer (LABC/MBC) pre-treated with at least two chemotherapy regimens. This article summarizes the review of evidence by the Evidence Review Group (ERG) and provides a summary of the NICE Appraisal Committee's (AC's) decision. The clinical evidence was derived from a multi-centred, open-label, randomized, phase III study comparing eribulin with treatment of physician's choice (TPC) in 762 patients with LABC/MBC. Clinical effectiveness results were submitted for two populations: the overall intention-to-treat (ITT) population and a subset (n = 488) that included only patients from North America, Western Europe and Australia (Region 1). For the primary endpoint of overall survival (OS), a primary analysis (after 55 % of patients had died) and an updated analysis (after 77 % of patients had died) were conducted. In the ITT population, treatment with eribulin was associated with a significant improvement in median OS compared with TPC in both primary [difference in median OS 2.5 months; hazard ratio (HR) 0.81, 95 % confidence interval (CI) 0.66-0.99] and updated analyses (2.7 months; HR 0.81, 95 % CI 0.67-0.96). A statistically significant improvement in progression-free survival (PFS) was reported for eribulin compared with TPC when assessed by the investigator (difference in median PFS 1.48 months; HR 0.76, 95 % CI 0.64-0.90), but not when assessed by the ERG (1.44 months; HR 0.87, 95 % CI 0.71-1.05). Gains in OS were greater for Region 1 patients than for the ITT population (3.1 vs. 2.7 months). Health-related quality of life (HRQoL) data suggested a benefit for eribulin responders, but was based on phase II studies. In the eribulin arm, serious adverse events included febrile neutropenia (4.2 %) and neutropenia (1.8 %), with peripheral neuropathy being the most common reason for treatment discontinuation. The manufacturer's economic evaluation using Patient Access Scheme costs reported a base-case incremental cost-effectiveness ratio (ICER) for eribulin versus TPC (Region 1) of £46,050 per quality-adjusted life year gained (corrected to £45,106 when an erroneous data entry was removed). The ERG's revised ICERs were £61,804 for Region 1 and £76,110 for the overall population. The AC concluded that the evidence

Topics: Antineoplastic Agents; Breast Neoplasms; Cost-Benefit Analysis; Disease-Free Survival; Female; Furans; Humans; Ketones; Neoplasm Metastasis; Quality of Life; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Survival Rate

The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of eribulin in patients with metastatic breast cancer are reviewed.. Classical chemotherapeutic agents for breast cancer have dominated treatment regimens even in the era of targeted therapy. Disease progression through these agents is often due to the development of resistance or lack of efficacy with these agents. Recently, a new nontaxane agent, eribulin mesylate, was approved for the treatment of metastatic breast cancer in patients who have received at least two prior chemotherapeutic agents. Eribulin is a member of a new class of synthetic cytotoxic agents derived from the Japanese sea sponge Halichondria okadai. Eribulin differs from other antimicrotubule agents in that it can bind to the microtubule cap and inhibit tubulin polymerization, leading to microtubule arrest. In Phase II clinical trials, eribulin demonstrated activity in extensively pretreated patients who had previously received an anthracycline, taxane, and capecitabine and had shown disease progression within the last six months of treatment. In a pivotal Phase III clinical trial of heavily pre-treated patients, patients who received eribulin versus the physician's treatment of choice showed a significant increase in overall and progression-free survival. Eribulin has a manageable adverse-effect profile, consisting mainly of neutropenia and fatigue. Eribulin has been associated with a low incidence of peripheral neuropathy.. Eribulin, a novel synthetic antimicrotubule agent that binds to the vinca domain of tubulin and inhibits the polymerization of tubulin, offers a new treatment option for metastatic breast cancer or locally advanced breast cancer.

Topics: Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Ethers, Cyclic; Female; Furans; Humans; Ketones; Macrolides; Neoplasm Metastasis

Treatment of metastatic breast cancer (MBC) remains one of the major challenges in cancer care. Chemotherapeutic agents currently approved for the treatment of invasive disease may exhibit initial efficacy; however, the development of resistance to therapy and concerns over tolerability are common and generally limit treatment options available to physicians and patients. Novel chemotherapeutic agents are, therefore, necessary to increase survival, delay disease progression, and improve tolerability. Eribulin mesylate (E7389) is a novel microtubule dynamics inhibitor with a unique mechanism of action that has shown antitumor efficacy and a manageable tolerability profile in clinical trials. Importantly, eribulin is the only single agent to date that has been shown to prolong overall survival in patients with heavily pretreated MBC. This review will discuss eribulin, with focus on the potential it has to address the specific treatment needs of patients with MBC who are refractory to conventional chemotherapies.

Topics: Animals; Breast Neoplasms; Clinical Trials as Topic; Disease Progression; Drug Resistance, Neoplasm; Female; Furans; Humans; Ketones; Mesylates; Neoplasm Metastasis; Survival; Treatment Outcome

Eribulin is a synthetic analog of halichondrin B, a non-taxane microtubule inhibitor extracted from the marine sponge, Halichondria okaida. It presents a novel mechanism of action and is active on cancer cells resistant to other antimicrotubule agents. It was granted approval in the USA and Europe for the treatment of heavily pretreated metastatic breast cancer. Early trials had shown activity in this setting with main toxicities being neutropenia and neuropathy in patients where quality of life is essential. Approvals were granted after a phase 3 trial demonstrated overall survival benefit in metastatic breast cancer previously treated with anthracyclines, taxanes, and capecitabine, in a setting where most treatments are failing to demonstrate a survival benefit. Recent data suggest that this survival benefit is also consistent in the elderly with no excess toxicity. Future strategies of eribulin are being tested in ongoing trials, evaluating this drug in earlier metastatic lines as well as in the adjuvant and the neoadjuvant settings.

Topics: Adult; Aged; Antineoplastic Agents; Breast; Breast Neoplasms; Clinical Trials as Topic; Drug Monitoring; Ethers, Cyclic; Female; Furans; Humans; Ketones; Macrolides; Microtubules; Neoplasm Metastasis; Neutropenia; Treatment Outcome

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Drug Administration Schedule; Drug Approval; Drug Discovery; Female; Furans; Humans; Infusions, Intravenous; Ketones; Neoplasm Metastasis; Treatment Outcome; Tubulin Modulators

Despite advances in cancer biology, chemotherapy remains the backbone of treatment approaches for many patients with metastatic breast cancer (MBC). Halichondrins, derived from marine sponges, have significant potential as potent antimicrotubule agents. Eribulin, with proven preclinical activity, is a synthetic halichondrin analog with novel actions on tubulin including suppression of microtubule polymerization. Phase I and II studies in MBC identified neutropenia as the dose-limiting toxicity and a maximum tolerated dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. An encouraging response rate of 11.5% in refractory MBC led to the launch of the phase III Eisai Metastatic Breast Cancer Study Assessing Physician's Choice versus Eribulin trial, in which heavily pretreated patients with MBC were randomized 2 : 1 to intravenous eribulin or monotherapy of the investigator's choice. Recently, it was reported that this important study of 762 patients met its primary endpoint of overall survival: eribulin was associated with an improvement in median overall survival from 10.65 months to 13.12 months (hazard ratio 0.8; 95% confidence interval 0.66-0.99) and a response rate of 12.2%. In general, the side effect profile of eribulin seems to be acceptable, as although neutropenia occurred in 45% of the patients, febrile neutropenia was rare and the incidence of neuropathy was low. These findings show that eribulin is potentially a new active agent for MBC, although results of ongoing studies are awaited to confirm the reported benefit. Future studies will investigate the potential role of eribulin in other settings, including for early breast cancer, to ascertain how to optimally incorporate this new agent into current treatment paradigms.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Clinical Trials, Phase III as Topic; Ethers, Cyclic; Female; Furans; Humans; Infusions, Intravenous; Ketones; Macrolides; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neutropenia; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome; Tubulin Modulators

Despite the recent trend toward treatment of early stage breast cancer aggressively with anthracyclines and taxanes, nearly half of those women will have metastatic recurrence. Moreover, because of the increasing prior exposure to these drugs, far more women facing first-line therapy for recurrent disease will now have developed anthracycline- and taxane-refractory metastatic breast cancer (ATRMBC), presenting a major therapeutic challenge. A number of established drugs are showing promise in this setting: capecitabine alone or combined with lapatinib; gemcitabine; vinorelbine; and oxaliplatin. At the same time, a variety of new drugs are emerging for potential use in ATRMBC. Among the drugs in clinical development that have shown promising activity include novel classes of compounds (camptothecins and epothilones), newer members of established classes (pemetrexed and vinflunine), and agents with novel mechanisms of action (the mitosis inhibitor E7389 and the ascidian-derived anticancer compound trabectedin). Several molecularly targeted agents are also being evaluated in ATRMBC, including interleukin-2 receptor-binding denileukin diftitox, and 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), which inhibits the protein chaperone heat shock protein 90.

Topics: Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Camptothecin; Clinical Trials as Topic; Deoxycytidine; Dioxoles; Diphtheria Toxin; Drug Resistance, Neoplasm; Drugs, Investigational; Epothilones; Female; Furans; Gemcitabine; Glutamates; Guanine; Humans; Interleukin-2; Ketones; Lapatinib; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Pemetrexed; Quinazolines; Recombinant Fusion Proteins; Tetrahydroisoquinolines; Trabectedin; Vinblastine; Vinorelbine

Metastatic breast cancer (MBC) is an incurable disease and its treatment focuses on prolonging patients' (pts) overall survival (OS) and improving their quality of life. Eribulin is a microtubule inhibitor that increases OS in pre-treated MBC pts. The most common adverse events (AEs) are asthenia, neutropenia and peripheral neuropathy (PN).. PAINTER is a single arm, phase IV study, aimed at evaluating the tolerability of eribulin in MBC pts. Secondary objectives were the description of treatment efficacy and safety, the assessment of the incidence and severity of PN and its association with genetic polymorphisms. Genomic DNA was isolated from blood samples and 15 Single Nucleotide Polymorphisms (SNPs) were genotyped by Taqman specific assays. The association between PN and SNPs were evaluated by Fisher exact test.. Starting from May 2014 until June 2018 180 pts were enrolled in this study by 20 Italian centers. 170 of these pts could be evaluated for efficacy and toxicity and 159 for polymorphisms analysis. The median age of pts was 60 years old and the biological subtypes were luminal type (64.7%), Her2 positive (18.3%) and triple negative (17%). Pts were pretreated with a median of 5 lines for MBC. The median follow up of this study was 15.4 months with a median number of 4.5 cycles administered (minimum-maximum 1-23). The median overall survival was 12 months. 48.8% of pts experienced a dose reduction, mainly for neutropenia (23.9%) and liver toxicity (12%). 65 pts (38.2%) reported at least one severe toxicity. Neutropenia and neurotoxicity were the most frequent severe AEs (15.3% and 14.7%, respectively); other reported toxicities were osteo-muscular, abdominal or tumor site pain (19.4%), liver toxicity (6.6%), pulmonary toxicity (6.5%) and dermatological toxicity (3.6%). Among the 15 evaluated SNPs, an association with PN was found for rs2233335 and rs7214723.. Eribulin is a well-tolerated treatment option in MBC. Schedule and dosage modifications were common, but toxicity rarely led to treatment discontinuation. SNPs rs2233335 (G/T and T/T) in the NDRG1 gene and rs7214723 (CC and CT) in the CAMKK1 gene were associated with PN. These findings, if validated, could allow a tailored treatment with eribulin in cancer patients.. ClinicalTrials.gov ID: NCT02864030.

Topics: Breast Neoplasms; Female; Humans; Middle Aged; Neoplasm Metastasis; Neutropenia; Peripheral Nervous System Diseases; Polymorphism, Genetic; Quality of Life; Treatment Outcome

Immune checkpoint inhibitors (ICIs) have minimal therapeutic effect in hormone receptor-positive (HR+ ) breast cancer. We present final overall survival (OS) results (n = 88) from a randomized phase 2 trial of eribulin ± pembrolizumab for patients with metastatic HR+ breast cancer, computationally dissect genomic and/or transcriptomic data from pre-treatment tumors (n = 52) for molecular associations with efficacy, and identify cytokine changes differentiating response and ICI-related toxicity (n = 58). Despite no improvement in OS with combination therapy (hazard ratio 0.95, 95% CI 0.59-1.55, p = 0.84), immune infiltration and antigen presentation distinguished responding tumors, while tumor heterogeneity and estrogen signaling independently associated with resistance. Moreover, patients with ICI-related toxicity had lower levels of immunoregulatory cytokines. Broadly, we establish a framework for ICI response in HR+ breast cancer that warrants diagnostic and therapeutic validation. ClinicalTrials.gov Registration: NCT03051659.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antigen Presentation; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Breast Neoplasms; Cytokines; Drug Resistance, Neoplasm; Estrogens; Female; Furans; Gene Expression Profiling; Genetic Heterogeneity; Genome, Human; Genomics; Humans; Immune Checkpoint Inhibitors; Ketones; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Mutation; Neoplasm Metastasis; Receptors, Estrogen; Receptors, Progesterone; Signal Transduction; Survival Rate; Treatment Outcome

Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician's choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile.. We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m. We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients.. Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Endothelial Cells; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Treatment Outcome

Eribulin methylate (eribulin) improved the overall survival (OS) of HER2-negative advanced breast cancer (HER2-ABC) patients; however, the mechanism underlying the OS improvement has not been clarified. Several reports suggest that eribulin promotes antitumor immunity via tumor micro-environment conditioning. Recently, a maintained baseline lymphocyte count was proposed as predictive marker for eribulin therapy in HER2-ABC patients; however, no associations with the OS have been noted. We retrospectively investigated the neutrophil-to-lymphocyte ratio and absolute lymphocyte count (ALC) in HER2-ABC patients receiving eribulin and assessed the utility of eribulin re-administration for further OS improvement.. HER2-ABC patients who received eribulin therapy at Shizuoka Cancer Center between November 2011 and December 2018 were retrospectively analyzed.. A total of 144 HER2-ABC (108 estrogen receptor-positive [ER+], 36 ER-) patients were identified, and 32 patients (28 ER+ , 4 ER-) were re-administered with eribulin. In the ER+ subgroup, a multivariate analysis showed that an ALC ≥ 1000/μL and re-administration were significantly associated with the OS (hazard ratio [HR] 0.503; P = 0.034 and HR 0.366; P < 0.0001, respectively), and an ALC ≥ 1000/μL was also identified as the only predictive factor for re-administration (HR 0.329; P = 0.033). In contrast, a multivariate analysis in the ER- subgroup identified no predictive markers.. In HER2-ER + ABC patients, ALC was identified as a predictive marker for eribulin therapy, and the re-administration of eribulin is considered a valid therapeutic option for further improvement of the OS.

Topics: Adult; Aged; Breast Neoplasms; Female; Follow-Up Studies; Furans; Humans; Ketones; Lymphocytes; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retreatment; Retrospective Studies; Survival Rate; Tumor Microenvironment

Combining bevacizumab with paclitaxel significantly improves progression-free survival (PFS) versus paclitaxel alone in HER2-negative metastatic breast cancer (MBC). Eribulin is active and tolerable in pretreated MBC. To assess whether eribulin may offer a more tolerable yet effective combination partner for bevacizumab, we evaluated a bevacizumab/eribulin combination regimen as first-line therapy for MBC.. The median age of the 61 treated female patients was 59 years, 16% had triple-negative MBC, 30% had ≥3 metastatic sites, and 71% had received prior (neo)adjuvant chemotherapy. Patients received a median of six eribulin and nine bevacizumab cycles. The non-progression rate at 1 year was 32% (95% confidence interval [CI]: 20-43%), ORR was 47% (95% CI: 34-60%), and median PFS was 8.3 months (95% CI: 7.0-9.6 months). The only grade ≥3 clinical adverse events in >5% of patients were hypertension (39%), neutropenia (26%), thrombosis (10%), and paresthesia/dysesthesia (7%).. First-line eribulin/bevacizumab combination therapy showed interesting activity in MBC with an acceptable safety profile, including a particularly low incidence of high-grade neuropathy.

Topics: Adult; Aged; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Disease Progression; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Treatment Outcome

The phase III OlympiAD study (NCT02000622) showed a statistically significant progression-free survival benefit with olaparib versus chemotherapy treatment of physician's choice (TPC) in patients with a germline BRCA mutation and human epidermal growth factor receptor 2-negative metastatic breast cancer. From this study, we report the effect of olaparib on health-related quality of life (HRQoL).. Patients were randomised 2:1 to olaparib monotherapy (300 mg twice daily) or single-agent TPC. The primary HRQoL end-point was mean change from baseline in the two-item global health status/QoL score determined from patient-completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module (EORTC QLQ-C30) questionnaires and assessed using a mixed model for repeated measures. Symptoms and functioning domains, best overall response and time to deterioration of QoL were also evaluated.. Overall questionnaire compliance rates were 93.2% for olaparib and 76.3% for TPC. Between-treatment global health status/QoL comparison showed a significant improvement in the olaparib arm versus the TPC arm, with mean change of 3.9 (standard deviation 1.2) versus -3.6 (2.2), a difference of 7.5 points (95% confidence interval [CI]: 2.48, 12.44; P = 0.0035). A higher proportion of patients in the olaparib arm showed a best overall response of 'improvement' in global health status/QoL (33.7% vs 13.4%). Median time to global health status/QoL deterioration was not reached in olaparib patients and was 15.3 months for TPC patients (hazard ratio: 0.44 [95% CI: 0.25, 0.77]; P = 0.004). For EORTC QLQ-C30 symptoms and functioning subscales, only nausea/vomiting symptom score was worse in the olaparib arm than in the TPC arm (across all visits compared with baseline).. HRQoL was consistently improved for patients treated with olaparib, compared with chemotherapy TPC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Capecitabine; Female; Follow-Up Studies; Furans; Germ-Line Mutation; Humans; International Agencies; Ketones; Male; Middle Aged; Neoplasm Metastasis; Patient Reported Outcome Measures; Phthalazines; Piperazines; Prognosis; Quality of Life; Receptor, ErbB-2; Survival Rate; Time-to-Treatment; Vinorelbine; Young Adult

Eribulin has efficacy in patients with progression after ≥ 1 chemotherapeutic regimen for metastatic breast cancer (MBC). A short disease-free interval (DFI) and previous use of taxanes in the neoadjuvant or adjuvant setting have been associated with worse outcomes for patients receiving first-line chemotherapy for HER2-negative MBC. The aim of the present trial was to evaluate the efficacy and safety of eribulin as first-line therapy for patients with HER2-negative MBC with these poor prognostic factors.. Eribulin monotherapy was administered until disease progression or unacceptable toxicity. The principal selection criteria were HER2 negativity without previous chemotherapy for MBC, the previous use of taxanes for early-stage breast cancer, and a DFI of < 36 months (subsequently amended to 48 months). The primary endpoint was the investigator-assessed time to progression. The secondary endpoints included overall survival, progression-free survival, objective response rate, clinical benefit rate, duration of response, and toxicity profile. A total of 53 patients were enrolled and received ≥ 1 dose of eribulin.. The median patient age was 47 years (range, 23-82.8 years). The median DFI was 15.7 months (range, 0.1-46.4 months). The median investigator-assessed time to progression was 4.1 months (range, 0.2-27.8 months; 95% confidence interval, 3.2-6.2 months). The objective response and clinical benefit rate was 20.8% and 26.4%, respectively. All-grade and grade 3/4 adverse events developed in 96.2% and 69.8% of patients, respectively. The most common treatment-related adverse events were neutropenia, leukopenia, alopecia, nausea, and anemia.. Eribulin is effective and safe as first-line therapy for aggressive taxane-pretreated HER2-negative MBC.

Topics: Adult; Aged; Aged, 80 and over; Antimitotic Agents; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Drug Resistance, Neoplasm; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Receptor, ErbB-2; Taxoids; Treatment Outcome; Young Adult

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Follow-Up Studies; Furans; Humans; Ketones; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis; Receptor, ErbB-2; Survival Rate; Trastuzumab

The E-VITA study evaluated the efficacy and tolerability of two schedules of eribulin and lapatinib in patients with trastuzumab-pretreated HER-2-positive metastatic breast cancer. This multicenter, open-label phase II trial, randomly assigned patients with trastuzumab-pretreated HER-2-positive metastatic breast cancer to lapatinib 1000 mg daily with eribulin 1.23 mg/m (equivalent to 1.4 mg/m eribulin mesylate) days 1+8 every 21 days (split-dose arm) or eribulin 1.76 mg/m (equivalent to 2.0 mg/m eribulin mesylate) day 1 every 21 days (3-weekly arm). Time to progression and tolerability were defined as primary end points; no sample size calculation for formal comparison of efficacy data has been performed. Secondary end points included objective response rate, clinical benefit rate, and overall survival. Overall, 43 patients of a planned number of 80 patients were recruited. At a median follow-up of 28.7 months, the median time to progression was 8.1 months [95% confidence interval (CI): 4.8-9.4] in the split-dose arm and 6.5 months (95% CI: 4.6-13.4) in the 3-weekly arm. Objective response rate was 52.4% (95% CI: 31.0-73.7) in the split-dose arm and 45.0% (95% CI: 23.2-66.8) in the 3-weekly arm, and clinical benefit rate was 71.4% (95% CI: 52.1-90.8) and 75.0% (95% CI: 56.0-94.0), respectively. Overall survival was also similar in both arms. The most frequent grade 3-4 adverse events were neutropenia (58.5%) and leukopenia (39.0%). The combination of eribulin and lapatinib showed an acceptable safety profile with less toxicity observed in the eribulin 1.23 mg/m day 1+8 group. This might be an alternative regimen when other treatment options are exhausted. Therefore, further clinical studies are warranted.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Female; Follow-Up Studies; Furans; Humans; Ketones; Lapatinib; Middle Aged; Neoplasm Metastasis; Prognosis; Receptor, ErbB-2; Salvage Therapy; Survival Rate; Trastuzumab

Eribulin mesylate is a nontaxane microtubule dynamics inhibitor approved for second-line (European Union) or third-line (United States) treatment of metastatic breast cancer. Two phase 2 single trials, evaluating first-line eribulin as monotherapy (Study 206; NCT01268150) or in combination with trastuzumab (Study 208; NCT01269346) in locally recurrent or metastatic breast cancer, demonstrated objective response rates of 28.6 and 71.2%, respectively. Median progression-free survival was 6.8 and 11.6 months, respectively. Tolerability profiles were similar to those from previous studies. This secondary analysis was conducted to assess health-related quality of life (HRQoL) in both phase 2 trials.. Of the 108 patients (56 in Study 206 and 52 in Study 208) treated, 57 and 87%, respectively, completed 6 cycles. Completion rates for both questionnaires were 94 and 98%, respectively, at cycle 6. Most patients had stable/improved HRQoL scores with some exceptions; for example, more patients experienced a worsening in cognitive functioning and systemic therapy side effects than experienced improvement. Mean QLQ-C30 symptom scores correlated with corresponding adverse event rates for nausea/vomiting, dyspnea, appetite loss, constipation, and diarrhea in Study 206 and for fatigue, nausea/vomiting, pain, dyspnea, insomnia, constipation, and diarrhea in Study 208.. First-line eribulin ± trastuzumab therapy did not lead to deterioration of overall HRQoL in most patients, with more than 60% of patients having stable/improved global health status/quality-of-life scores. Eribulin has been demonstrated to be comparable with other chemotherapy agents with an acceptable safety profile. Therefore, further evaluation is warranted to determine whether eribulin ± trastuzumab therapy may be a potential option for first-line treatment in some patients with metastatic breast cancer who were recently treated in the neoadjuvant setting.. NCT01268150 (December 29, 2010), NCT01269346 (January 4, 2011).

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Quality of Life; Surveys and Questionnaires; Survival Analysis; Trastuzumab; Treatment Outcome

Combining sorafenib and eribulin mesylate may provide synergistic antitumor activities with limited overlapping toxicities. This phase 1b, open-label, dose-escalation study evaluated safety, pharmacokinetics, maximum tolerated dose/recommended phase 2 dose (MTD/RP2D), and preliminary efficacy of sorafenib plus standard-dose eribulin mesylate in patients with advanced, metastatic, or refractory tumors. Patients received sorafenib 200 mg twice daily (BID; n = 5), 600 mg/day (n = 8), and 400 mg BID (MTD; n = 27). Dose-limiting toxicities were increased alanine aminotransferase and acute coronary syndrome (both grade 3) in the 400-mg BID dose-escalation and expansion cohorts, respectively. No significant increase in mean QTcF duration was observed with eribulin plus sorafenib versus eribulin alone; there were no drug-drug interactions. Five patients achieved partial response; 16 achieved stable disease. The combination of sorafenib and eribulin mesylate presented no unexpected safety concerns and no significant impact on QT/QTc intervals or drug-drug interactions. Sorafenib 400 mg BID plus standard-dose eribulin is the RP2D.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Furans; Humans; Ketones; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Prognosis; Salvage Therapy; Sorafenib; Survival Rate; Young Adult

The C-X-C chemokine receptor type 4 (CXCR4)-stromal cell-derived factor-1α (SDF-1α) axis regulates function and trafficking of immune cells and the tumour microenvironment. CXCR4 antagonists have been shown to enhance the activity of different anticancer treatments in preclinical models. We assessed the safety, tolerability, pharmacokinetics, and preliminary phase 1 activity of the CXCR4 antagonist, balixafortide, in combination with eribulin chemotherapy in patients with heavily pretreated, relapsed metastatic breast cancer.. The safety and tolerability of balixafortide plus eribulin seems to be similar to that of eribulin or balixafortide monotherapy, and the preliminary activity of the combination seems promising in patients with HER-negative metastatic breast cancer. The results suggest that balixafortide plus eribulin has potential to provide a new therapeutic option in heavily pretreated patients with metastatic breast cancer and warrants further investigation in randomised trials.. Polyphor.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Female; Furans; Humans; Ketones; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Peptides, Cyclic; Receptor, ErbB-2; Receptors, CXCR4; Spain; Time Factors; Treatment Outcome; United States

Eribulin mesylate is currently indicated as a sequential monotherapy to be administered after two chemotherapeutic regimens, including anthracycline and taxane treatments, for treatment of metastatic breast cancer. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of eribulin as a first- or second-line treatment for patients with metastatic breast cancer.. Between December 2012 and September 2015, 32 patients with metastatic breast cancer were enrolled at 10 participating clinical institutions in Japan, and toxicity and response rates were evaluated. The overall response rate was 43.8% (95% confidence interval [CI] 26.5-61.0). The clinical benefit and tumor control rates were 56.3% (95% CI 39.0-73.5) and 78.1% (95% CI 63.8-92.5), respectively. Median progression-free survival was 8.3 months (95% CI 7.1-9.4). A subgroup analysis did not identify any factors affecting the efficacy of eribulin. The most common adverse events were neutropenia (71.9%), alopecia (68.7%), and peripheral neuropathy (46.9%). As a first- or second-line therapy, eribulin showed sufficient efficacy for metastatic breast cancer compared with taxane and capecitabine treatment in previous clinical trials. The safety profile of eribulin was acceptable.. Eribulin may be another option for first-line chemotherapeutic regimens for metastatic breast cancer.. This trial was retrospectively registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (ID number: UMIN000010334 ). Date of trial registration: April 1st, 2013.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis

Inflammation affects tumor immune surveillance and resistance to therapy. Here, we show that production of IL1β in primary breast cancer tumors is linked with advanced disease and originates from tumor-infiltrating CD11c

Topics: Animals; Breast Neoplasms; Capecitabine; CD11c Antigen; Cell Line, Tumor; Cell Membrane; Female; Furans; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Ketones; Leukocytes, Mononuclear; Macrophages; Mice; Mice, SCID; Myeloid Cells; Neoplasm Metastasis; Neoplasm Transplantation; Paclitaxel; Pilot Projects; Transcription, Genetic; Transforming Growth Factor beta

Although eribulin mesylate(ERI)has been approved for metastatic breast cancer, its efficacy and safety in combination with other chemotherapeutic agents have not been established. To investigate the tolerability of combination therapy with ERI and gemcitabine(GEM), we conducted a phase I clinical study in Japanese patients with metastatic breast cancer. The initial doses(Level 0)of ERI and GEM were 1.1mg/m2 and 800 mg/m2, respectively. When tolerability to Level 0 doses was confirmed, the doses were escalated to 1.4mg/m2 for ERI and 800 mg/m2 for GEM(Level 1). Seven patients were enrolled in this study; 3 patients received Level 0 doses and the other 4 patients received Level 1 doses. A dose limiting toxicity(DLT)was found in only 1 patient of the Level 1 group(Grade 3 oral mucositis). However, Grade 3 or higher hematological toxicities, including neutropenia, frequently occurred, and hence, this combination therapy was not conducted as scheduled. Thus, maximum tolerated dose(MTD)and recommended dose(RD)for phase II trials were not evaluated in this study. Drugdrug interactions between ERI and GEM were not observed. In conclusion, it was difficult to continue the combination therapy for patients with advanced recurrent breast cancer due to hematological toxicities. There is little possibility for the combination therapy with ERI and GEM at the specific doses to be regarded as a new treatment option for Japanese patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Deoxycytidine; Drug Administration Schedule; Female; Furans; Gemcitabine; Humans; Ketones; Middle Aged; Neoplasm Metastasis

Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies. However, the development of CTCs as a predictive marker for treatment effects on breast cancer remains an enormous task. We investigated CTCs, including epithelial mesenchymal transition (EMT) status, from metastatic breast cancer patients who had received eribulin-based treatment, which reportedly suppresses EMT as a means of tumour suppression. Our aim was to test the possibility of this method serving as a tool predicting eribulin efficacy.. Twenty-two patients were enrolled and peripheral blood samples were collected before eribulin treatment. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Progression-free survival (PFS) and clinical response were assessable in 20 and 18 patients, respectively, in relation to the number of CTCs.. Numbers of total CTCs were significantly increased in patients with progressive disease during treatment (p = 0.006). Median PFS was 14.6 weeks and patients with more total and mesenchymal CTCs at baseline had significantly shorter PFS (p = 0.0013 and 0.013, respectively). Multivariate logistic regression analysis revealed small number of total baseline CTCs and long disease-free survival to be related to long PFS (p = 0.0004 and 0.020, respectively).. Our data suggest that determining both mesenchymal and epithelial CTCs at baseline might be a good tool for predicting eribulin responsiveness. Evaluation of mesenchymal CTC can be considered as a parameter in larger studies, while most clinical trials are currently employing only the detection of the epithelial cellular adhesion molecule (EpCAM).

Topics: Adult; Aged; Breast Neoplasms; Cell Size; Disease-Free Survival; Epithelial-Mesenchymal Transition; Female; Furans; Humans; Kaplan-Meier Estimate; Ketones; Logistic Models; Middle Aged; Neoplasm Metastasis; Neoplastic Cells, Circulating; Pilot Projects; Treatment Outcome

Quality of life (QoL) is a critical issue for women with metastatic breast cancer (MBC). Eribulin mesylate represents a novel and active drug for pretreated MBC. Regretfully, few data exploring health-related (HR) QoL are available in unselected populations.. A multicenter prospective observational study was conducted in 50 MBC patients treated with eribulin mesylate, in order to evaluate HRQoL and patients' well-being by using the Edmonton symptoms assessment scale (ESAS) and Functional Assessment of Cancer Therapy-Breast questionnaires.. A significant ESAS score improvement was observed with a 10% median decrease. No differences were revealed for the QoL scores.. The analysis of ESAS and Functional Assessment of Cancer Therapy scores showed that eribulin mesylate contributes to preserve QoL in MBC patients.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Prospective Studies; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Paclitaxel plus gemcitabine (PG) combination chemotherapy is a preferred chemotherapeutic regimen for patients with metastatic breast cancer (MBC). Eribulin mesylate is a halichondrin non-taxane inhibitor of microtubule dynamics. A recent pooled analysis with eribulin showed improved overall survival (OS) in various MBC patient subgroups pretreated with anthracycline and taxane. Furthermore, eribulin may have less neurotoxicity than paclitaxel.. This study was a prospective randomised phase II, open-label, two-arm, multicentre study comparing eribulin plus gemcitabine (EG) with PG chemotherapy as a first-line treatment for patients with human epidermal growth factor receptor 2-negative MBC. We hypothesised that EG chemotherapy would not be inferior to PG chemotherapy. The primary end-point was progression-free survival (PFS), which was estimated to be 70% at 6 months for each arm. The secondary end-points were as follows: OS, neuropathic scale, toxicity and clinical benefit rate.. A total of 118 patients (median age: 50, 24-66) were enrolled between March 2015 and March 2016 and were randomly assigned to PG (n = 59) or EG (n = 59) chemotherapy. The mean number of metastatic sites was 3 (range 1-8). The 6-month PFS rates for both arms were 72% for EG and 73% for PG (P = 0.457). There was no significant difference in OS between the two groups (not reached versus 21.2 months, P = 0.2234). The median number of chemotherapy cycles for both groups was 10 for EG and 8 for PG (range 2-32). Clinical benefit rates were 44% for EG and 49% for PG. Major toxicities were neutropenia and neurotoxicity. Grade II or above neurotoxicity was more common with PG than with EG (13.6% for EG versus 45.8% for PG, P < 0.0001).. EG chemotherapy had similar clinical benefits to PG chemotherapy in terms of PFS but less neurotoxicity.. KCSG BR13-11; ClinicalTrials.gov, NCT02263495.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Deoxycytidine; Disease-Free Survival; Female; Furans; Gemcitabine; Humans; Kaplan-Meier Estimate; Ketones; Middle Aged; Neoplasm Metastasis; Paclitaxel; Proportional Hazards Models; Prospective Studies; Receptor, ErbB-2; Republic of Korea; Time Factors; Treatment Outcome; Young Adult

Eribulin mesilate was approved for the treatment of patients with locally advanced or metastatic breast cancer (MBC), who had received at least two chemotherapeutic regimens, including anthracycline and taxane. On the other hand, the efficacy and safety information of eribulin in Korean patients is limited by the lack of clinical trials.. In this multicenter, open-label, single-arm, phase IV study, locally advanced or MBC patients were enrolled between June 2013 and April 2014 from 14 centers in Korea. One point four mg/m. A total of 101 patients received at least one dose of eribulin and were included in the safety set. The patients received a total of 543 treatment cycles, with a median of three cycles (range, 1 to 31 cycles). The most common adverse event was neutropenia (91.1% of patients, 48.3% of cycles). The frequent non-hematological adverse events included alopecia, decrease in appetite, fatigue/asthenia, and myalgia/arthralgia. The peripheral neuropathy of any grade occurred in 27 patients (26.7%), including grade 3 in two patients. Disease control rate was 52.7% and 51.3% of patients in the full analysis set and per-protocol set, respectively.. This study demonstrated the feasible safety profile and activity of eribulin in Korean patients with MBC.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Combined Modality Therapy; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Republic of Korea; Retreatment; Treatment Outcome

Despite the survival benefit and acceptable tolerability of eribulin for advanced/metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes, there is limited evidence of the clinical benefit of early eribulin use. We investigated the efficacy and safety of first- to third-line eribulin use in patients with MBC.. In this phase II, open-label, single-arm study conducted at 14 sites in Kyushu, Japan, women with histologically confirmed human epidermal growth factor receptor 2-negative MBC were enrolled between December 1, 2011 and November 30, 2013 (Data cut-off: November 30, 2014). Objective response rate (ORR; primary endpoint), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety were evaluated.. Of 53 recruited patients, 47 were enrolled. The ORR was 17.0% (95% confidence interval, 7.6-30.8), DCR was 66.0% (51.2-77.8), median PFS was 4.9 months (3.5-7.0), DOR was 6.6 months (1.9-14.3), and median OS was 17.4 months (10.1-not evaluable). The common grade 3/4 adverse events were neutropenia (25 patients; 53.2%), leucopenia (16 patients; 42.1%) and febrile neutropenia (4 patients; 8.5%). Toxicity did not increase during the long-term treatment. Subgroup analysis indicated that first-line treatment led to higher ORR and prolonged PFS and OS than second-/third-line treatment and that incidence of adverse events in patients of second-/third-line treatment was not higher than that in patients of first-line treatment.. Eribulin exhibited efficacy and manageable tolerability in Japanese women with pretreated MBC in first- to third-line use. (ID: UMIN000007121).

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Confidence Intervals; Disease-Free Survival; Female; Furans; Humans; Japan; Ketones; Middle Aged; Neoplasm Metastasis; Neutropenia; Taxoids; Time Factors; Treatment Outcome

Eribulin, a microtubule dynamics inhibitor, is approved for the treatment of patients with breast cancer and soft tissue sarcoma. We investigated the efficacy and safety of eribulin in Japanese patients with soft tissue sarcoma.. This open-label, multicenter, nonrandomized, Phase 2 study enrolled Japanese patients with measurable, advanced/metastatic soft tissue sarcoma of high/intermediate grade and ≥1 prior chemotherapy for advanced disease. Patients received eribulin mesilate 1.4 mg/m2 intravenously over 2–5 minutes on Days 1 and 8 of a 21-day cycle. The primary endpoint was progression-free rate at 12 weeks. Secondary endpoints included overall survival, progression-free survival and safety. Efficacy analyses were stratified by histology (liposarcoma or leiomyosarcoma, and other subtypes).. Overall, 52 patients were enrolled and 51 patients were treated. Patients with liposarcoma/leiomyosarcoma (n = 35) had similar characteristics to those with other subtypes (n = 16), except for a higher proportion of women (63% vs 38%, respectively) and patients with Eastern Cooperative Oncology Group performance status 0 (57% vs 44%). Progression-free rate at 12 weeks was 60% in liposarcoma/leiomyosarcoma patients, 31% in other subtypes and 51% overall. Median progression-free survival was 5.5 months in liposarcoma/leiomyosarcoma patients, 2.0 months in other subtypes and 4.1 months overall. Median overall survival was 17.0 months in liposarcoma/leiomyosarcoma patients, 7.6 months in other subtypes and 13.2 months overall. The most common Grade 3–4 adverse events were neutropenia (86%), leukopenia (75%), lymphopenia (33%), anemia (14%) and febrile neutropenia (8%).. Eribulin showed clinical activity with a manageable safety profile in previously treated Japanese patients with advanced/metastatic soft tissue sarcoma.

Topics: Adult; Aged; Disease-Free Survival; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Sarcoma; Treatment Outcome

Eribulin is a non-taxane microtubule dynamics inhibitor that showed a survival benefit versus treatment of physician's choice in a phase III trial enrolling patients with metastatic breast cancer (MBC).. The E7389-G000-398 trial was designed to provide eribulin to MBC patients pre-treated with anthracylines, taxanes and capecitabine. Patient characteristics, efficacy and safety data were collected prospectively. Efficacy and survival analyses were performed using retrospectively collected data of patients treated at a single institution.. One hundred fifty-four patients were enrolled and the median number of previous lines of chemotherapy was 4. The most frequent adverse events were fatigue/asthenia (74%), alopecia (55%), peripheral neuropathy (46%) and neutropenia (43%). Objective response rate (ORR) was 24% in the evaluable population and 14% in patients pre-treated with both taxanes and vinorelbine. In patients with oestrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)- MBC, response rate was 29% and 21% with triple-negative disease. Activity was minimal in HER2+ MBC treated with eribulin monotherapy (14% ORR). Median progression-free survival was 3.2 months. Median overall survival was 11.3 months; 77% of patients were alive at 6 months and 43% at 12 months.. Eribulin was active in MBC patients with a high tumour burden and predominant visceral disease. Safety profile was similar to what was reported in the phase III trials. Prophylactic granulocyte colony-stimulating factor administration allowed optimal dose intensity and could have contributed to the recorded response rate. Activity is sustained after treatment with taxanes and vinorelbine. The recently investigated combination of eribulin and trastuzumab should lead to higher activity in HER2-positive MBC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Treatment Outcome

No clinical evidence on the efficacy and safety of eribulin monotherapy has been obtained by a prospective clinical study in patients with metastatic breast cancer (MBC) who had well-defined taxane resistance. The present Phase II, multicenter, single-arm, open-label study aimed to obtain the evidence. Japanese female patients, aged 33-74 years who had the metastasis of taxane-resistant and histopathologically confirmed breast cancer, received eribulin mesylate 1.4 mg/m(2) (equivalent to eribulin 1.23 mg/m(2) [expressed as free base]) as a 2- to 5-min intravenous infusion on days 1 and 8 of each 21-day cycle. The primary endpoint was the clinical benefit rate (CBR) [complete response (CR), partial response (PR), and long-term stable disease (LSD) ≥24 weeks]. A total of 51 patients underwent chemotherapy cycles (median 4; range 1-42 cycles). The CBR was 39.2 % (CR 2.0 %; PR 23.5 %; and LSD 13.7 %), and the rate of progressive disease was 49.0 %. The median progression-free survival and the median overall survival were 3.6 months [95 % confidence interval (CI) 2.6-4.6 months] and 11.7 months (95 % CI 9.2-14.2 months), respectively. Grade 3 or greater adverse events were leukopenia (23.5 %), neutropenia (35.3 %), anemia (5.9 %), and febrile neutropenia (7.8 %). The incidences of grade 3 and 4 peripheral sensory neuropathy were 2.0 and 0 %, respectively. Eribulin showed a clinically manageable tolerability profile by dose adjustments or symptomatic treatment. Eribulin was effective and well tolerated in heavily pretreated patients with MBC who had well-defined taxane resistance, thus providing a potential therapeutic option in the clinical settings.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Drug Administration Schedule; Female; Furans; Humans; Infusions, Intravenous; Japan; Ketones; Middle Aged; Neoplasm Metastasis; Prospective Studies; Survival Analysis; Treatment Outcome

We evaluated the safety, maximum-tolerated dose (MTD), pharmacokinetics, recommended dose for phase II (P2RD), and preliminary anticancer activity of a combination eribulin and S-1 therapeutic in metastatic breast cancer patients pretreated with anthracycline and taxane.. Patients aged 20-74 years were recruited. In level 1, patients received S-1 (65 mg m(-2)) from day 1 to 14, and eribulin (1.1 mg m(-2)) on day 1 and 8 in a 21-day cycle. In level 2, eribulin was increased to 1.4 mg m(-2). In level 3, S-1 was increased to 80 mg m(-2).. Twelve patients were enrolled into three cohorts. Planned dose escalation was completed, with one case exhibiting dose-limiting toxicity (grade 3 hypokalaemia) at level 3, without reaching the MTD. The P2RD was determined to be level 2 (eribulin 1.4 mg m(-2) and S-1 65 mg m(-2)). The most common grade 3 or 4 toxicity was neutropenia (83.3%), followed by febrile neutropenia (25.0%). Five of eleven patients (41.7%) with measurable disease had a partial response. Pharmacokinetics were characterised by dose-dependent elimination and nonlinear exposure.. Dose level 3 was not tolerated owing to febrile neutropenia development. Thus, intermediate dose level 2 was recommended for further evaluation. Preliminary antitumour activity warrants further investigation in this setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Furans; Humans; Ketones; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Tegafur; Young Adult

Eribulin mesylate is a synthetic microtubule inhibitor that showed cytotoxic synergy in combination with gemcitabine preclinically. This combination was assessed in a Phase I dose-finding trial in patients diagnosed with advanced solid tumours who had received up to two prior chemotherapy regimens for metastatic disease (CP cohort).. Dose escalation was performed in a 3+3 design to identify the recommended phase II dose (RP2D). Two additional expansion cohorts in women with gynaecologic cancers at the RP2D (G), and further dose escalation of metastatic chemotherapy-naive patients (CN), were evaluated.. 45 patients were treated: 21 (CP), 10 (G) and 14 (CN). The initial combination of eribulin and gemcitabine was administered on days 1, 8, and 15 of a 28-day cycle; however, due to 2 out of 6 dose-limiting haematological toxicities at the first dose level, a reduced dose-intense schedule was assessed. The RP2D was defined at 1.0 mg m(-2) eribulin and 1000 mg m(-2) gemcitabine day 1 and 8 q3 weeks. No other significant toxicities were observed in the G expansion cohort. Neutropenia prevented further dose escalation in the CN cohort. Objective responses were seen in all three cohorts - 2/21 (CP), 1/10 (G) and 2/14 (CN).. The combination of eribulin and gemcitabine was well tolerated at the RP2D.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease-Free Survival; Endometrial Neoplasms; Female; Furans; Gemcitabine; Humans; Ketones; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Neutropenia; Ontario; Ovarian Neoplasms; Response Evaluation Criteria in Solid Tumors; Treatment Outcome

Following the demonstrated efficacy and safety of eribulin mesylate in heavily pretreated patients with metastatic breast cancer, an exploratory analysis was performed to investigate the effect of age in these patients.. Data were pooled from two single-arm phase II studies and one open-label randomized phase III study in which patients received eribulin mesylate at 1.4 mg/m(2) as 2- to 5-minute intravenous infusions on days 1 and 8 of a 21-day cycle. The effect of age on median overall survival (OS), progression-free survival (PFS), overall response rate (ORR), clinical benefit rate (CBR), and incidence of adverse events (AEs) was calculated for four age groups (<50 years, 50-59 years, 60-69 years, ≥ 70 years). RESULTS. Overall, 827 patients were included in the analysis (<50 years, n = 253; 50-59 years, n = 289; 60-69 years, n = 206; ≥ 70 years, n = 79). Age had no significant impact on OS (11.8 months, 12.3 months, 11.7 months, and 12.5 months, respectively; p = .82), PFS (3.5 months, 2.9 months, 3.8 months, and 4.0 months, respectively; p = .42), ORR (12.7%, 12.5%, 6.3%, and 10.1%, respectively), or CBR (20.2%, 20.8%, 20.4%, and 21.5%, respectively). Although some AEs had higher incidence in either the youngest or the oldest subgroup, there was no overall effect of age on the incidence of AEs (including neuropathy, neutropenia, and leukopenia).. Eribulin monotherapy in these selected older patients with good baseline performance status led to OS, PFS, ORR, CBR, and tolerability similar to those of younger patients with metastatic breast cancer. The benefits and risks of eribulin appear to be similar across age groups.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Retrospective Studies; Treatment Outcome

Eribulin mesylate, a novel non-taxane microtubule dynamics inhibitor, is approved for treatment of metastatic breast cancer (MBC) in patients who have previously received at least 2 chemotherapeutic regimens for MBC that should have included an anthracycline and a taxane in the adjuvant or metastatic setting. This phase 2 study evaluated efficacy and safety of eribulin as first-line therapy for human epidermal growth factor receptor 2-negative (HER2-negative) MBC. Patients with measurable HER2-negative locally recurrent breast cancer or MBC with ≥12 months since prior neoadjuvant or adjuvant (neo/adjuvant) chemotherapy received eribulin mesylate 1.4 mg/m(2) IV on days 1 and 8 of each 3-week cycle. Endpoints included objective response rate (ORR) per RECIST v1.1 (primary), safety, progression-free survival (PFS), clinical benefit rate (ORR + stable disease ≥6 months; CBR), and duration of response (DOR). Fifty-six patients were enrolled and received eribulin; 38 (68 %) had prior neo/adjuvant therapy, including 33 who had anthracycline and/or taxane-containing chemotherapy; 41 (73 %) had estrogen receptor-positive disease, and 12 (21 %) had estrogen receptor-negative, progesterone receptor-negative, and HER2-negative (triple-negative) disease. Patients received a median of 7 cycles (range 1-43); 6 (11 %) received treatment for ≥12 months. ORR was 29 % (95 % CI 17.3-42.2), CBR was 52 %, and median DOR was 5.8 months. Median PFS was 6.8 months. Thirty-six patients (64 %) had grade 3/4 treatment-related adverse events; most common were neutropenia (50 %), leukopenia (21 %), and peripheral neuropathy (21 %). These results demonstrate that eribulin has substantial antitumor activity as first-line treatment for HER2-negative MBC with acceptable safety.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Receptor, ErbB-2; Treatment Outcome

The aim of this study was to assess efficacy and safety of eribulin with trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer.. In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2+ breast cancer received eribulin mesylate at 1.4 mg/m(2) intravenously (I.V.) on days 1 and 8 of each 21-day cycle with an initial trastuzumab dose of 8 mg/kg I.V. on day 1, followed by 6 mg/kg of trastuzumab on day 1 of each subsequent cycle. Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 12 weeks thereafter. The primary end point was ORR, and secondary end points included PFS, TTR, DOR, and safety.. Fifty-two patients were enrolled. Fifty-one patients (98.1%) had metastatic disease, 25 (48.1%) with liver metastases, 24 (46.2%) with lung metastases, and 19 (36.5%) with bone metastases. Patients received a median of 10.0 cycles of eribulin and 11.0 cycles of trastuzumab. The ORR was 71.2% (n = 37) with median TTR of 1.3 months, DOR of 11.1 months, and PFS of 11.6 months. The most common Grade 3/4 treatment-emergent adverse events were neutropenia in 20 (38.5%) patients, peripheral neuropathy in 14 (26.9%; all Grade 3) patients, fatigue in 4 (7.7%) patients, and febrile neutropenia in 4 (7.7%) patients.. Because of the high ORR, prolonged median PFS, and acceptable safety profile, combination eribulin/trastuzumab is an acceptable treatment option for locally recurrent or metastatic HER2+ breast cancer.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Female; Follow-Up Studies; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Receptor, ErbB-2; Survival Rate; Trastuzumab

Data from two phase 3 studies of eribulin were pooled in analyses initially requested by the European Medicines Agency to assess whether specific patient subgroups, previously treated with an anthracycline and a taxane, benefited from eribulin. Study 305/EMBRACE included women after two-to-five lines of chemotherapy for advanced breast cancer who were randomized to eribulin mesylate (1.4 mg/m(2) on days 1 and 8 every 21 days) or treatment of physician's choice. In Study 301, patients who had received up to two prior chemotherapy regimens for advanced disease were randomized to eribulin (as above) or capecitabine (1.25 g/m(2) b.i.d. on days 1-14 every 21 days). In the pooled population, overall survival (OS), progression-free survival and response rates were analysed in the intent-to-treat population and selected subgroups. Overall, 1,062 patients were randomized to eribulin and 802 patients to control. Median OS was 15.2 months with eribulin versus 12.8 months with control (hazard ratio [HR] 0.85; 95% CI 0.77, 0.95; P = 0.003). In all subgroups assessed, OS data favoured eribulin; significant improvements occurred in some subgroups, notably in women with human epidermal growth factor receptor 2 (HER2)-negative disease (HR 0.82; P = 0.002), although the effect in those with HER2-negative but hormone-receptor-positive disease did not reach statistical significance; benefits were also seen, among others, in those with estrogen-receptor-negative and triple-negative disease. Eribulin improves OS in various patient subgroups with advanced/metastatic breast cancer who had previously received an anthracycline and a taxane. Women with HER2-negative disease are among those who may obtain benefit from eribulin.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Receptor, ErbB-2; Taxoids

Peripheral neuropathy is a common toxicity associated with tubulin-targeted chemotherapeutic agents. This Phase II study compares the incidence and severity of neuropathy associated with eribulin mesylate or ixabepilone in metastatic breast cancer (MBC). The primary objective was to assess the incidence of neuropathy; the study was designed to detect a difference in neuropathy rate of 35 % for eribulin versus 63 % for ixabepilone (odds ratio 0.316, 80 % power, 0.05 two-sided significance level). Eligibility criteria included: MBC; prior taxane therapy; at least one chemotherapy for advanced disease; no or minimal pre-existing neuropathy (Grade 0 or 1). The intent-to-treat population comprised 104 patients randomized (1:1) to eribulin mesylate (1.4 mg/m(2), 2-5 min intravenous on days 1 and 8) or ixabepilone (40 mg/m(2), 3 h intravenous on day 1) on a 21-day cycle. 101 patients in the safety population received a median of 5.0 eribulin and 3.5 ixabepilone cycles. Incidence of neuropathy (any grade) was 33.3 and 48.0 %, and peripheral neuropathy was 31.4 and 44.0 % for eribulin and ixabepilone, respectively. After controlling for pre-existing neuropathy and number of prior chemotherapies, these differences were not significant. Compared with ixabepilone, fewer patients receiving eribulin discontinued treatment due to neuropathy (3.9 vs. 18.0 %) or adverse events (AEs) in general (11.8 vs. 32.0 %). Time to onset of neuropathy was 35.9 weeks for eribulin and 11.6 weeks for ixabepilone, and time to resolution was 48 versus 10 weeks, respectively; other AEs were comparable. Objective responses were 15.4 versus 5.8 % and clinical benefit rates were 26.9 versus 19.2 %. In conclusion, after controlling for pre-existing neuropathy and number of prior chemotherapies, the differences in the incidence of neuropathy with eribulin and ixabepilone were not statistically significant. Onset of neuropathy tended to occur later with eribulin and resolve later.

Topics: Adult; Breast Neoplasms; Epothilones; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Peripheral Nervous System Diseases; Survival Rate

Treatment options remain limited for patients with castration-resistant prostate cancer (CRPC). We evaluated eribulin mesylate (E7389), a nontaxane halichondrin B analog microtubule inhibitor, in patients with metastatic CRPC with or without previous taxane exposure.. Men with histologically proven CRPC, with or without prior taxane exposure, were enrolled in an open-label, single-arm phase II trial. Patients received eribulin mesylate 1.4 mg/m(2) as a 2- to 5-min i.v. bolus infusion on days 1 and 8 of a 21-day cycle. The primary efficacy end point was prostate-specific antigen (PSA) response rate.. In total, 108 patients were assessable for safety (50 were taxane-pretreated) and 105 for efficacy in the per-protocol population. The median age of patients was 71 years and median number of cycles was 4. PSA decreases of ≥ 50% were achieved in 22.4% and 8.5% of taxane-naive and taxane-pretreated patients, respectively. The most common grade 3/4 adverse event was neutropenia, seen in 22.4% of chemo-naive and 40% of taxane-pretreated men. Grade 3 peripheral neuropathy occurred in none of the taxane-naive patients and 6.0% of taxane-pretreated patients.. Eribulin mesylate demonstrated activity and a relatively favorable toxicity profile in metastatic CRPC.

Topics: Aged; Aged, 80 and over; Algorithms; Antineoplastic Agents; Carcinoma; Chemotherapy, Adjuvant; Drug Resistance, Neoplasm; Furans; Humans; Ketones; Male; Middle Aged; Neoplasm Metastasis; Orchiectomy; Patient Selection; Prostatic Neoplasms; Taxoids; Treatment Failure; Treatment Outcome

Eribulin mesylate, an halichondrin B analog, binds to tubulin and microtubules and possesses broad anti-cancer activity. We conducted a multi-institutional Phase II trial to evaluate the response rate of eribulin mesylate in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN).. Forty eligible patients who had not received prior chemotherapy for metastatic or recurrent SCCHN were enrolled with the following characteristics: 29 male, 11 female; median age 61.2 years; Zubrod Performance Status of 0 (48%) and 1 (53%). Thirty-three patients (83%) had metastatic disease. Primary tumor sites included: 38% oropharynx, 30% lip/oral cavity, 15% larynx, 10% hypopharynx, 5% other/unknown and 3% nasopharynx. Patients received eribulin mesylate at 1.4 mg/m² on Days 1 and 8 of an every 21-day cycle.. Common Grade 3 and 4 toxicities included: lymphopenia (15%), leukocytopenia (13%), neutropenia (10%), hyponatremia (5%), fatigue (5%), diarrhea (5%) and dyspnea (5%), with one treatment-related death due to pulmonary hemorrhage. Among 40 assessable patients, two confirmed partial responses were observed, for an estimated confirmed response rate of 5% (95% confidence interval: 1-17%). The estimated median progression-free survival is 3 months (95% confidence interval: 1-3 months) and estimated median overall survival is 7 months (95% confidence interval: 5-10 months).. Eribulin mesylate given on Days 1 and 8 of a twenty-one day cycle in metastatic or recurrent SCCHN was well tolerated, but did not result in a clinically significant median PFS. Studies of other agents should be considered in this setting.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Furans; Head and Neck Neoplasms; Humans; Ketones; Male; Middle Aged; Neoplasm Metastasis; Treatment Outcome

Treatments with survival benefit are greatly needed for women with heavily pretreated metastatic breast cancer. Eribulin mesilate is a non-taxane microtubule dynamics inhibitor with a novel mode of action. We aimed to compare overall survival of heavily pretreated patients receiving eribulin versus currently available treatments.. In this phase 3 open-label study, women with locally recurrent or metastatic breast cancer were randomly allocated (2:1) to eribulin mesilate (1·4 mg/m(2) administered intravenously during 2-5 min on days 1 and 8 of a 21-day cycle) or treatment of physician's choice (TPC). Patients had received between two and five previous chemotherapy regimens (two or more for advanced disease), including an anthracycline and a taxane, unless contraindicated. Randomisation was stratified by geographical region, previous capecitabine treatment, and human epidermal growth factor receptor 2 status. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00388726.. 762 women were randomly allocated to treatment groups (508 eribulin, 254 TPC). Overall survival was significantly improved in women assigned to eribulin (median 13·1 months, 95% CI 11·8-14·3) compared with TPC (10·6 months, 9·3-12·5; hazard ratio 0·81, 95% CI 0·66-0·99; p=0·041). The most common adverse events in both groups were asthenia or fatigue (270 [54%] of 503 patients on eribulin and 98 [40%] of 247 patients on TPC at all grades) and neutropenia (260 [52%] patients receiving eribulin and 73 [30%] of those on TPC at all grades). Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in 24 (5%) of 503 patients.. Eribulin showed a significant and clinically meaningful improvement in overall survival compared with TPC in women with heavily pretreated metastatic breast cancer. This finding challenges the notion that improved overall survival is an unrealistic expectation during evaluation of new anticancer therapies in the refractory setting.. Eisai.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Survival Rate

Eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor, is a structurally simplified, synthetic analog of the marine natural product halichondrin B. This open-label, single-arm, phase II study evaluated efficacy and tolerability of eribulin in heavily pretreated patients with metastatic breast cancer (MBC).. MBC patients who were previously treated with an anthracycline and a taxane received eribulin mesylate (1.4 mg/m(2)) as a 2- to 5-minute intravenous (IV) infusion on days 1, 8, and 15 of a 28-day cycle. Because of neutropenia (at day 15), an alternative regimen of eribulin on days 1 and 8 of a 21-day cycle was administered. The primary end point was overall response rate.. Of the 103 patients treated, the median number of prior chemotherapy regimens was four (range, one to 11 regimens). In the per-protocol population (n = 87), eribulin achieved an independently reviewed objective response rate (all partial responses [PRs]) of 11.5% (95% CI, 5.7 to 20.1) and a clinical benefit rate (PR plus stable disease > or = 6 months) of 17.2% (95% CI, 10.0 to 26.8). The median duration of response was 171 days (5.6 months; range, 44 to 363 days), the median progression-free survival was 79 days (2.6 months; range, 1 to 453 days), and the median overall survival was 275 days (9.0 months; range, 15 to 826 days). The most common drug-related grades 3 to 4 toxicities were as follows: neutropenia, 64%; leukopenia, 18%; fatigue, 5%; peripheral neuropathy, 5%; and febrile neutropenia, 4%.. Eribulin demonstrated activity with manageable tolerability (including infrequent grade 3 and no grade 4 neuropathy) in heavily pretreated patients with MBC when dosed as a short IV infusion on days 1 and 8 of a 21-day cycle.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Ethers, Cyclic; Female; Furans; Humans; Ketones; Macrolides; Microtubules; Middle Aged; Neoplasm Metastasis; Taxoids; Treatment Outcome

The achievement of complete response with chemotherapy after multiple treatment lines in metastatic breast cancer and the chemosensitivity in a luminal-like breast cancer are two important issues as it is often asked whether there is a potential limit to the number of therapeutic lines offered and what clinical value they may have. In this setting, eribulin mesylate is a chemotherapy option available. Several randomized and observational studies demonstrated eribulin's meaningful improvement on prolongation of survival, chronicling the disease and preventing the onset of new metastases, although the rate of complete responses is rather limited.. We report the five-year history of a luminal A breast cancer, stage IV at diagnosis, metastasized to bone and brain. After undergoing four chemotherapy lines and several radiotherapy sessions with partial response as the best response on bone and with a complete response on brain, our patient finally achieved a metabolic complete response also on bone after about a year of fifth-line treatment with eribulin. Currently the patient is in close clinical and radiological follow-up.. This case report aims to emphasize the clinical value of a chronic chemotherapy treatment also in heavily pretreated and luminal-like metastatic breast cancer, supporting eribulin as a good choice to consider.

Topics: Antineoplastic Agents; Brain; Breast Neoplasms; Female; Furans; Humans; Ketones; Neoplasm Metastasis

A predictive marker for efficacy of eribulin administered as different lines of treatment in metastatic breast cancer (MBC) has not been identified. We aimed to determine the predictive factors for efficacy of eribulin administered as different lines of treatment in MBC patients.This restrospective cohort study included 49 heavily pre-treated MBC patients who received either eribulin monotherapy or combination therapy with eribulin and anti-Her2 therapy. Associations between clinical response of eribulin-based treatment, time-to-treatment failure (TTF), and possible predictive markers were investigated.Patients' median age was 55 years; 65% were ER+; 43% were HER2+; and 16% were triple-negative. Median TTF was 5.23 months and longer in non-visceral metastases patients. Eastern Cooperative Oncology Group (ECOG) status was 0-1; eribulin as ≥2nd-line treatment; eribulin combined with dual blockades; lymphocyte-monocyte ratio (LMR) ≥3; and monocyte-lymphocyte ratio (MLR) <0.4. In patients with eribulin as >3rd-line treatment, univariate analysis showed that ECOG status was 0-1, and LMR ≥3 and MLR <0.4 were associated with a low risk of TTF. Multivariate analysis showed that ECOG status 0-1 was an independent protective factor. Leukopenia and neutropenia were the most common manageable adverse events.ECOG status is an independent predictor for TTF, while LMR and MLR may have an interactive effect with other biomarkers (e.g., ECOG status) to predict response in MBC patients receiving eribulin as ≥2nd-line treatment.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Cohort Studies; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Prognosis; Retrospective Studies; Treatment Outcome

To compare the real-world effectiveness and costs of eribulin to those of capecitabine in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes.. This study extracted data from the Health and Welfare Database in Taiwan to identify MBC patients, and then eribulin and capecitabine users were matched at a 1:1 ratio by age, residential region, Charlson Comorbidity Index score, and molecular subtype of BC cell. The overall survival (OS) and time-to-treatment discontinuation (TTD) curves were plotted using the Kaplan-Meier method. Healthcare utilization and costs between the two groups were compared.. A total of 24,550 MBC patients were identified, and 298 patients were enrolled in each group after matching. The median OS was 11.8 months for eribulin (95%CI: 11.5-13.5 months) and 15.2 months for capecitabine (95%CI: 15.3-17.9 months; HR = 1.7, p < 0.0001). The median TTD was 4.0 months for eribulin and 6.6 months for capecitabine (HR = 1.6; p < 0.0001). No significant difference was found between the two groups in patients with >4 prior chemotherapy agents (OS: HR 1.1, 95%CI 0.8-1.5; TTD: HR 1.2, 95%CI 0.9-1.7). The total healthcare costs per patient during the treatment period were NT$580,523.8 for eribulin versus NT$497,223.8 for capecitabine (p < 0.0001), and total medication costs were NT$438,335.8 and NT$348,438.4 (p < 0.0001), respectively.. Although eribulin showed an attenuated effect in the real-world setting in Taiwan, it may serve as an alternative for capecitabine in a heavy pretreated population. The total healthcare and medication costs were found to be higher with eribulin treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Capecitabine; Cost-Benefit Analysis; Drug Costs; Female; Furans; Health Care Costs; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Quality of Life; Taiwan; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Furans; Humans; Ketones; Neoplasm Metastasis; Salivary Ducts; Salivary Gland Neoplasms

Systemic treatments for advanced soft tissue sarcoma are limited. Eribulin showed activity in metastatic soft tissue sarcoma, particularly liposarcomas. Data from six patients with advanced liposarcoma that received eribulin as third- or fourth-line therapy are presented herein. Eribulin treatment was well tolerated; no grade 3-4 toxicity or therapy delay was observed. Two patients had a partial response; four had a prolonged stable disease. The first case, with pre-existing chronic renal dysfunction, achieved a 6-month stable disease with dose-reduced eribulin. The second case became resectable after eribulin treatment, with a 6-month complete surgical remission. The third case obtained a 7-month stable disease with eribulin and stereotactic body radiotherapy. The last three cases were ≥65 years old, and two of them had objective response with eribulin.

Topics: Aged; Antineoplastic Agents; Biomarkers; Female; Furans; Humans; Ketones; Liposarcoma; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Renal Insufficiency, Chronic; Retreatment; Tomography, X-Ray Computed; Treatment Outcome

We report the case of a 51 year-old patient affected by an advanced uterine leiomyosarcoma treated with eribulin as fourth-line therapy. The patient, with a previous history of leiomyomas of the myometrium, had undergone total hysterectomy for repeated metrorrhagias. After 7 years, metastases in the liver, bone and lung were documented. A fine needle liver biopsy demonstrated leiomyosarcoma metastasis. The patient was treated with first-line doxorubicin chemotherapy; after six cycles, disease progression was observed. A second-line trabectedin chemotherapy and a third-line gemcitabine chemotherapy were performed; no objective responses were seen after two cycles. The patient was then treated with eribulin on the basis of an EORTC Phase II trial showing preliminary activity in uterine leiomyosarcoma. After six cycles, CT scan showed partial remission of liver lesion. Disease progression was observed after nine cycles with eribulin, without severe side effects and preserving a good quality of life.

Topics: Antineoplastic Agents; Biopsy; Bone Marrow; Female; Furans; Humans; Ketones; Leiomyosarcoma; Magnetic Resonance Imaging; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Tomography, X-Ray Computed; Treatment Outcome

Topics: Breast Neoplasms; Female; Furans; Humans; Ketones; Lymphocyte Count; Lymphocytes, Tumor-Infiltrating; Neoplasm Metastasis; Treatment Outcome

In the present study, the breast cancer patient-derived orthotopic xenograft (PDOX) model was used to identify an effective drug for a highly aggressive triple negative breast cancer (TNBC).. The TNBC tumor from a patient was implanted in the right 4th inguinal mammary fat pad of nude mice to establish a PDOX model. Three weeks later, 19 mice were randomized into the untreated-control group (n=10) and the eribulin treatment group (n=9, eribulin, 0.3 mg/kg, i.p., day 1).. On day 8, eribulin significantly inhibited tumor volume compared to the control group (p<0.01). Eribulin regressed tumors in 3 mice (33.3%) and apparently eradicated them in 6 mice (66.7%). At day 14, tumor regrowth was observed in 2 mice of the eribulin group, which was undetectable on day 8. However, 44.4% (4 out of 9) of the mice in the eribulin group were tumor-free on day 14.. A single low-dose eribulin was efficacious on a highly aggressive TNBC. The breast cancer PDOX model can be used to identify highly effective drugs for TNBC.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Disease Models, Animal; Disease Progression; Furans; Histocytochemistry; Humans; Ketones; Mice; Neoplasm Metastasis; Triple Negative Breast Neoplasms; Tumor Burden; Xenograft Model Antitumor Assays

Prior pooled analysis of eribulin studies (301 and 305) indicated eribulin prolonged overall survival (OS) in patients with locally advanced/metastatic breast cancer (MBC) regardless of visceral or nonvisceral disease. This hypothesis-generating post hoc analysis examined the efficacy of eribulin according to the location of metastatic sites at baseline in 1864 pretreated patients with locally advanced/MBC from studies 301 and 305. Analyses included OS, progression-free survival (PFS), and objective response rate; OS and PFS were also analyzed according to estrogen-receptor status. Eribulin appeared efficacious in patients with locally advanced/MBC, irrespective of the location of metastases at baseline. A nominally significant difference in OS in favor of patients randomized to eribulin compared with control in patients with bone, lymph node, and chest wall/breast/skin metastases at baseline was observed. Additionally, a difference in OS was also seen in patients with liver metastases randomized to eribulin versus control (median: 13.4 versus 11.3 months, respectively; hazard ratio, 0.84 [95% CI: 0.72, 0.97]). Results of this exploratory analysis suggest that eribulin may be efficacious for the treatment of locally advanced/MBC for patients with bone, liver, lung, lymph node, and chest wall/breast/skin metastases.

Topics: Adult; Antineoplastic Agents; Bone and Bones; Breast; Breast Neoplasms; Clinical Trials, Phase III as Topic; Female; Follow-Up Studies; Furans; Humans; Ketones; Liver; Lung; Lymph Nodes; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Prognosis; Progression-Free Survival; Randomized Controlled Trials as Topic; Risk Factors; Skin

The median survival time of patients with advanced soft tissue sarcoma (STS) is typically <12 months. Since 2012, physicians were able to administer second- and/or third-line treatment easily in Japan, following the approval of new drugs, namely, pazopanib, eribulin, and trabectedin. We investigated the real-life experience of adults with advanced STS who received systemic therapy after the approval of the aforementioned new drugs.. We retrospectively evaluated 34 patients (median age: 66 years) with primary STS arising at the extremities/trunk or unresectable local and/or metastatic STS between 2012 and 2019. We evaluated the tumor response and patient survival after initial systemic treatment.. As first-line treatment, doxorubicin and ifosfamide and other drugs were administered to 7 and 27 patients, respectively. Of 31 patients with an evaluable tumor response, partial response was observed in 2 (6.5%) patients, and 16 (52%) patients showed stable disease at 8 weeks. The 1- and 2-year survival rates were 51.4% and 28.4%, respectively. The median overall survival (OS) time was 12.6 months. Tumor response to first-line therapy was related to patient prognosis.. New drugs may be beneficial for patients with advanced STS. When patients cannot receive anthracycline-based chemotherapy because of a high risk of side effects, we believe that the aforementioned drugs may be administered as the first-line treatment.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Female; Furans; Humans; Indazoles; Japan; Kaplan-Meier Estimate; Ketones; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Pyrimidines; Retrospective Studies; Sarcoma; Soft Tissue Neoplasms; Sulfonamides; Survival Analysis; Trabectedin; Treatment Outcome

The identification of biomarkers for predicting the responsiveness to eribulin in patients with metastatic breast cancer pretreated with an anthracycline and a taxane remains an unmet need. Here, we established a serum microRNA (miRNA)-based prediction model for the emergence of new distant metastases after eribulin treatment. Serum samples were collected from metastatic breast cancer patients prior to eribulin treatment and comprehensively evaluated by miRNA microarray. The prediction model for estimating eribulin efficacy was established using the logistic LASSO regression model. Serum samples were collected from 147 patients, of which 52 developed at least one new distant metastasis after eribulin monotherapy and 95 did not develop new distant metastases. A combination of eight serum miRNAs (miR-4483, miR-8089, miR-4755-3p, miR-296-3p, miR-575, miR-4710, miR-5698 and miR-3160-5p) predicted the appearance of new distant metastases with an area under the curve of 0.79, sensitivity of 0.69 and specificity of 0.82. The serum levels of miR-8089 and miR-5698 were significantly associated with overall survival after the initiation of eribulin treatment. The present study provides evidence that serum miRNA profiling may serve as a biomarker for the responsiveness to eribulin and for predicting the development of new distant metastases in metastatic breast cancer.

Topics: Adult; Aged; Breast Neoplasms; Female; Furans; Humans; Ketones; MicroRNAs; Middle Aged; Neoplasm Metastasis; Prognosis; Treatment Outcome

Pneumothorax has been reported as a pazopanib-associated adverse event in patients with lung metastases of soft tissue sarcoma (STS). However, pneumothorax triggered by eribulin treatment has never been reported. We herein report two cases of spontaneous pneumothorax in patients with STS treated with eribulin. Both patients experienced pneumothorax accompanied by sudden dyspnea on day 9 or 10 of eribulin treatment. These two cases suggest that spontaneous pneumothorax may occur as an adverse event of eribulin treatment in such patients. We should therefore be alert for the potential development of pneumothorax during eribulin treatment of patients with STS and lung metastases.

Topics: Adult; Aged; Biopsy; Female; Furans; Humans; Ketones; Lung Neoplasms; Male; Neoplasm Metastasis; Pneumothorax; Sarcoma; Tomography, X-Ray Computed

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Neoplasm Metastasis; Treatment Outcome

Eribulin is approved for advanced breast cancers refractory to anthracyclines and taxanes. Efficacy according to sensitivity to previous therapies has been poorly explored.. Safety data were collected prospectively and we retrospectively collected efficacy data from the five French centres that participated in the Eribulin E7389-G000-398 expanded access program. Our main objectiveswere exploration of safety and analysis of eribulin efficacy (progression-free survival [PFS] and overall survival [OS]) according to sensitivity to the last microtubule-inhibiting agent administered.. Median eribulin treatment duration was 3.3 months for the 250 patients included in this prospective single-arm study. Two hundreds and thirty-nine patients (95.6%) experienced an adverse event (AE) related to treatment including 129 (51.6%) with grade ≥ 3 AEs. The most frequently observed toxicities were cytopenias (59.6% of included patients), gastrointestinal disorders (59.2%), and asthenia (56.4%). The most frequent grade 3-4 AE was neutropenia (37.2% with 4.8% febrile neutropenia). Median PFS and OS were 4.6 and 11.8 months, respectively. Patients classified as responders to the last microtubule-inhibiting therapy had a longer OS (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.51 to 0.94; p=0.017), and tended to display a better PFS (HR, 0.78; 95% CI, 0.58 to 1.04; p=0.086). OS improvement was still significant in multivariate analysis (adjusted HR, 0.53; 95% CI, 0.35 to 0.79; p=0.002).. This work based on a prospective study suggests that identification of patients likely to be more sensitive to eribulin could be based on their previous response to microtubules inhibitors.

Topics: Adult; Aged; Breast Neoplasms; Female; France; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Progression-Free Survival; Prospective Studies; Retrospective Studies; Survival Analysis; Treatment Outcome; Tubulin Modulators

Numerous patient- and disease-related factors must be considered when deciding a treatment approach for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Hormone therapy (HT) is generally the first option in the absence of compelling reasons for chemotherapy (e.g., rapidly progressive visceral disease). After failure of first-choice HT, alternative HT options are usually attempted until hormone resistance occurs and chemotherapy becomes the treatment of choice. The first two patients presented herein experienced prolonged disease control with third-line eribulin after two lines of HT. The third report involves a case of male breast cancer which typically presents as the HR+/HER2- phenotype. Eribulin in the second line provided prolonged clinical improvement and was well tolerated.

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Breast Neoplasms, Male; Carcinoma, Ductal, Breast; Female; Furans; Humans; Ketones; Male; Middle Aged; Neoplasm Metastasis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone

The aim of this study was to confirm the therapeutic role of eribulin on Taiwanese women with metastatic breast cancer.. This retrospective study examined 449 females who received eribulin between March 2014 and June 2017 at 14 hospitals in Taiwan for treatment of locally advanced or metastatic breast cancer.. The survival rate at 24 months was 57.2% (95% CI 51.0-62.9%) and the median time to treatment failure (TTF) was 3.91 months (95% CI 3.45-3.94). A total of 175 patients (40.1%) received eribulin for fewer than 90 days and the others received it for 90 days or more. Eight patients (1.83%) had complete remission, 82 (18.8%) had partial remission, 202 (46.3%) had stable disease, and 144 (33.0%) had progressive disease (PD). Patients' tumors with the luminal A subtype had a significantly better objective response rate. Kaplan-Meier analysis indicated that hormone receptor positivity, luminal A subtype, receipt of eribulin as the 1st to 3rd line therapy, and metastasis to fewer than 4 organs were significantly associated with longer TTF. Stepwise multivariate analysis showed that only receipt of eribulin as the 1st to 3rd line therapy was significantly associated with TTF (HR 1.49, p < 0.001). All toxicities were manageable and only 18 patients (4.1%) discontinued treatment due to adverse events.. Eribulin appears to have better efficacy and cause fewer adverse events, especially neutropenia, in Taiwanese women than Western women.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Drug Administration Schedule; Female; Furans; Humans; Kaplan-Meier Estimate; Ketones; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Proportional Hazards Models; Retrospective Studies; Taiwan; Treatment Outcome; Young Adult

Despite the wide pharmacological armamentarium available for the treatment of metastatic breast cancer (MBC), long-lasting control of disease is challenging, especially in heavily pretreated patients. In this case report, we documented a long-lasting complete response (CR) with eribulin in a relatively young woman with MBC and bone metastasis, who did not benefit from prior chemotherapy regimens. Besides CR, the patient was able to maintain an excellent performance status and was free from the severe pain experienced before the initiation of eribulin. Noteworthy, eribulin treatment was very well tolerated, with only a mild alopecia being reported; response was maintained also after a temporary dose interruption and a therapeutic holiday due to non-treatment-related increase in liver enzymes and steatosis.

Topics: Antineoplastic Agents; Breast; Breast Neoplasms; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Treatment Outcome

Topics: Antimitotic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Neoplasm Metastasis

Liver metastases are very common in metastatic breast cancer (MBC); current treatments for these lesions are based on systemic chemotherapy, endocrine- or human epidermal growth factor receptor 2 (HER2)-targeted therapy, and palliative therapy. However, no standard approach has been clearly identified for second and further chemotherapy lines in MBC patients. In the phase III clinical trial EMBRACE, eribulin was particularly effective in reducing liver lesions and improving both overall survival and progression-free survival in liver MBC patients. In this series, we collected 8 case reports of Italian clinical practice in which eribulin has shown significant efficacy in reducing liver metastases in MBC patients: complete response was reported in 2 patients, and 4 patients achieved partial response. The treatment was well tolerated, thus confirming that eribulin is a suitable therapeutic option for elderly patients and for those who have metastatic HER2-negative disease. In the setting of MBC, the sequencing of therapeutic agents should consider expected response, side effects, tumor characteristics, and patient's preferences, in order to successfully tailor the most appropriate therapy beyond earlier lines.

Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Female; Furans; Humans; Ketones; Liver; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Receptor, ErbB-2

Real-world data are critical to demonstrate the consistency of evidence and external generalizability of randomized controlled trials (RCTs). This study examined characteristics and outcomes of metastatic triple-negative breast cancer (mTNBC) patients treated with eribulin mesylate at community oncology practices in the United States.. Physicians identified mTNBC patients initiating eribulin between 1 January 2011 and 1 January 2014 and abstracted data into an electronic case report form (eCRF). Eribulin treatment in the metastatic setting was categorized as early use (EU, first-/second-line) and late use (LU, third-line or later). Patient characteristics, overall survival (OS), disease response (per treating physician), and adverse events (AEs) rates in each group, respectively, are reported.. Overall 252 eCRFs were completed: 125 (49.6%) EU and 127 (50.4%) LU. The median age at metastatic diagnosis was 53 years and 42.1% were stage IV at their initial diagnosis. The median duration of follow-up from the initiation of first-line treatment was 24 months. Rates of disease response (complete or partial per treating physician) were 69.9% in the EU group and 48.8% in the LU group. The five most commonly reported adverse events during eribulin were as follows: fatigue (65.1%), weakness (40.1%), decreased appetite (32.5%), neutropenia (31.0%), and leukopenia (27.4%). Discontinuation of eribulin due to AE was observed in 4.0% of patients. Median OS from initiation of eribulin was 23.0 months (95% CI: 18.7-27.3) among EU and 14.7 (95% CI: 12.6-16.9) among LU.. In the real-world eribulin-treated mTNBC, patients have more sites of metastatic disease and exposure to greater numbers of prior therapies compared to RCTs. The median OS of 14.7 months among LU patients is consistent with, and slightly longer than the 13.1 months and 14.4 months reported in the EMBRACE and Study 301 clinical trials, respectively.

Topics: Adult; Aged; Antineoplastic Agents; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Survival Analysis; Treatment Outcome; Triple Negative Breast Neoplasms; United States

The neutrophil lymphocyte ratio is reported to be a poor prognostic factor in each carcinoma, and the possibility of predicting the therapeutic effect of chemotherapy, for example, is being studied. In this study, we measured the NLR before and after administration of eribulin and the NLR before and after the final administration in breast cancer patients and examined the relationship with the therapeutic effect.. Eleven primary breast cancer patients were examined after eribulin was administered; PD was confirmed eventually, and administration was discontinued. The NLR was determined before the first administration of eribulin and 7 days after the administration; the NLR before the final administration and after the last administration were each tested with p<0.05 as the significance level and using the t test.. The average value of NLR before initial administration was 4.07±2.11, and the average value after 7 days of administration was 2.47±1.97. The NLR before initial administration tended to be higher, and a significant difference was observed(p<0.05). The average NLR value before the final administration was 4.02±2.04, and the average value of the NLR after the final administration was 3.19 ±1.76, showing no significant difference(p=0.27, NS).

Topics: Breast Neoplasms; Disease Progression; Furans; Humans; Ketones; Lymphocyte Count; Lymphocytes; Neoplasm Metastasis; Neutrophils; Recurrence

During the last decades, much effort has been made to develop and test treatments for advanced/metastatic breast cancer (MBC) able to prolong survival and improve patients' quality of life. In this regard, eribulin represents one of the most recent and interesting discoveries. This tubulin-targeting chemotherapy demonstrated a survival benefit in MBC women who progressed after at least two prior lines of chemotherapy for the treatment of metastatic disease (prior therapies should have included an anthracycline and a taxane, in either adjuvant or metastatic setting). Here, we described five cases of heavily pretreated MBC patients who experienced long-lasting control of disease with eribulin.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Positron-Emission Tomography; Retreatment; Tomography, X-Ray Computed; Treatment Outcome

Anthracycline- or taxane-based regimens are commonly used in the treatment of breast cancer, often in the (neo)adjuvant and first-line metastatic settings. However, to date, there is no single accepted standard of care after failure of these cytotoxic agents. Following the promising results obtained in the Phase III EMBRACE study, eribulin mesylate was approved for the treatment of metastatic breast cancer patients after progression with anthracyclines and taxanes unless contraindications. This case report describes a chemo-pretreated woman with important pleural effusion, nodal, locoregional involvement from breast cancer who had a disease response after treatment with eribulin in second line. This case underlines how this well-tolerated monochemotherapy may be able to obtain a prolonged disease control and a good clinical outcome.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Combined Modality Therapy; Comorbidity; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Retreatment; Treatment Outcome

This study evaluates efficacy, tolerability and health-related quality of life of eribulin in patients with metastatic breast cancer. Predictive and/or prognostic factors of outcome were also analyzed. Among 44 women receiving eribulin mesylate, one patient had a complete response, 22.7% a partial response and 25% a stable disease. Median overall survival and median progression-free survival were 11.8 and 4.5 months, respectively. Treatment was well tolerated; the most frequent adverse events were neutropenia (52%), leukopenia (50%), fatigue (38%) and alopecia (40%). No significant reductions of health-related quality of life parameters were observed. Disease control during previous chemotherapy lines was related with better outcome with eribulin. In conclusion, eribulin treatment should be considered in a multiple chemotherapy lines strategy in metastatic breast cancer.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Female; Furans; Humans; Kaplan-Meier Estimate; Ketones; Middle Aged; Neoplasm Metastasis; Quality of Life; Retreatment; Retrospective Studies; Treatment Outcome

The halichondrin B analog, eribulin, exerts an anticancer effect, as reported by several clinical and real-life studies on metastatic breast cancer patients. Here, we evaluated efficacy and safety of eribulin, focusing on response to treatment per metastasis type.. This monocentric, real-life study was conducted on 31 heavily pretreated patients with metastatic breast cancer.. The median progression-free survival and overall survival were 2.0 and 5.5 months, respectively. All patients (12.9%) responding to eribulin were treated in fourth-line setting. Considering response per metastasis type, bone lesions (13.6%) responded more frequently than other metastases to eribulin.. Eribulin exhibited a good overall response rate, with the highest response observed for bone metastases.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Disease Progression; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Retreatment; Treatment Outcome

The cytotoxic agent, eribulin represents a new standard of care in the treatment of heavily pretreated metastatic breast cancer patients. Here, we describe our experience with eribulin in a patient with a controlled primary breast cancer, who showed an aggressive recurrence of the primary tumor, including metastatic disease. Treatment management of the second primary tumor included six lines of chemotherapy and three lines of hormonal therapy, including eribulin as sixth line among all chemotherapies received. Eribulin treatment achieved a fast response to all metastatic sites and decelerated the aggressive evolution of the second disease.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Female; Furans; Humans; Ketones; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Neoplasms, Second Primary; Retreatment; Tomography, X-Ray Computed

The antimitotic agent eribulin, a synthetic analog of halichondrin B isolated from a marine sponge, resulted particularly effective in improving the overall survival of heavily pretreated metastatic breast cancer (MBC) patients in randomized Phase III clinical trials and real-life studies. However, only scant information is available on the clinical experiences of patients who underwent long-lasting eribulin treatment followed by a rechallenge. Here we presented two cases of MBC women previously treated with several lines of chemotherapy and hormonal therapies, who underwent long-lasting treatment and rechallenge with eribulin, showing a partial response in both periods. These anecdotal experiences suggest that rechallenge with eribulin could represent a treatment strategy for advanced MBC and it should be evaluated in a larger study.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Drug Substitution; Female; Furans; Humans; Ketones; Neoplasm Metastasis; Neoplasm Staging; Retreatment; Tomography, X-Ray Computed; Treatment Outcome

Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Follow-Up Studies; Furans; Humans; Japan; Ketones; Middle Aged; Neoplasm Metastasis; Product Surveillance, Postmarketing; Treatment Outcome

Evidence of eribulin therapy for metastatic breast cancer (MBC) in clinical practice is not well documented.. We retrospectively analyzed the safety and efficacy of eribulin in 29 MBC patients from 2011 to 2016 at Fukuoka University Hospital.. Eribulin is effective for MBC patients who have received multiple chemotherapies. Neutropenia and febrile neutropenia may develop after heavy prior therapy.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Drug Administration Schedule; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Retrospective Studies; Treatment Outcome

Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker.. TILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively.. Of the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063).. The results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.

Topics: Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Disease Progression; Female; Furans; Humans; Ketones; Lymphocytes, Tumor-Infiltrating; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Treatment Outcome; Triple Negative Breast Neoplasms

Eribulin has shown survival advantage and manageable toxicity in heavily pre-treated metastatic breast cancer (mBC). We assessed whether body mass index (BMI) impacts treatment outcomes in 101 patients treated with eribulin at six Italian Oncologic Centers. BMI was addressed as a categorical variable (18.5-24.9 vs. at least 25). Clinical benefit rate (CBR) was assessed overall and in subgroups defined by BMI, line of therapy (LOT), and hormone receptor (HR) status. Analysis of CBR by LOT and HR status were further stratified by BMI. Survival curves were compared using the Kaplan-Meier method and log-rank test. Predictors of survival were tested in Cox models. Patients treated with eribulin as third line showed greater CBR when their BMI was in the lowest category (77.8 vs. 58.1%, P = 0.03). Median progression free survival (PFS) and overall survival (OS) in normal and overweight patients were 4 (95% CI, 3-5) versus 3 (2.1-4) months, P = 0.02 and 13 (11-15) versus 12 (6-18) months, P = 0.96, respectively. Median PFS and OS in estrogen receptor (ER) positive and negative tumours were 4 (3-5) versus 3 (2-4) months, P = 0.005 and 14 (10-18) versus 7 (4-10), P = 0.02, respectively. In multivariate analyses, BMI impacted PFS at a nearly significant extent (P = 0.05), while ER expression significantly affected PFS and OS (P = 0.01 and 0.02, respectively). No relevant findings emerged concerning toxicity. We found evidence of greater efficacy of eribulin in leaner mBC patients, particularly if given as third line and in ER positive tumors. Further studies are warranted to confirm our findings.

Topics: Adult; Aged; Body Mass Index; Breast Neoplasms; Disease-Free Survival; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Receptors, Estrogen; Treatment Outcome

There is currently no standard therapy for women with metastatic or locally recurrent breast cancer. The microtubule polymerization inhibitor eribulin, approved in March 2011, is the first monochemotherapy with a proven survival benefit and tolerable toxicity in this patient group. Using a retrospective analysis of 27 mostly heavily pretreated patients in two large German breast cancer centers, the efficacy and tolerability of eribulin in daily practice were compared with the results of the pivotal EMBRACE and 301 studies. Despite the patients being older and having more advanced disease, the retrospective analysis showed a comparable progression-free survival of 3.7 months. When eribulin was used in an early-line treatment, the progression-free survival observed was 7 weeks longer compared with use in a late-line therapy. The differences in tolerability were not significant. Overall, the results confirm that eribulin represents an effective and tolerable therapeutic option for metastatic breast cancer in daily practice.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Retrospective Studies

Based on data from two multicenter, phase III clinical trials (Studies 301 and 305), eribulin (a microtubule dynamics inhibitor) is indicated in the European Union (EU) for patients with locally advanced or metastatic breast cancer (MBC) after ≥1 prior chemotherapy for advanced disease, including an anthracycline and a taxane in either the adjuvant or metastatic setting. Data from Studies 305 and 301 were pooled to investigate the efficacy of eribulin in various subgroups of patients who matched the EU label, including those with human epidermal growth factor receptor 2 (HER2)-negative and triple-negative disease.. In Study 305 (NCT00388726), patients were randomized 2:1 to eribulin mesylate 1.4 mg/m(2) (equivalent to eribulin 1.23 mg/m(2) [expressed as free base]) intravenously on days 1 and 8 every 21 days] or treatment of physician's choice after 2-5 prior chemotherapies (≥2 for advanced disease), including an anthracycline and a taxane (in early/advanced setting). In Study 301 (NCT00337103), patients were randomized 1:1 to eribulin (as above) or capecitabine (1.25 g/m(2) orally twice daily on days 1-14 every 21 days) following ≤3 prior chemotherapies (≤2 for advanced disease), including an anthracycline and a taxane. Efficacy end points were investigated in the intent-to-treat population and subgroups, pooled as discussed above.. Overall, 1644 patients were included (eribulin: 946; control: 698); baseline characteristics were well matched. Overall survival was significantly longer with eribulin versus control (P < 0.01), as were progression-free survival and clinical benefit rate (both P < 0.05). Significant survival benefits with eribulin versus control were observed in a wide range of patient subgroups, including HER2-negative or triple-negative disease (all P < 0.05).. Our findings underline the survival benefit achieved by eribulin used according to EU label in the overall MBC population and in various subgroups of interest, including patients with HER2-negative and triple-negative disease.

Topics: Adjuvants, Pharmaceutic; Anthracyclines; Antineoplastic Agents; Bridged-Ring Compounds; Clinical Trials, Phase III as Topic; Disease-Free Survival; Female; Furans; Humans; Ketones; Neoplasm Metastasis; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Taxoids; Triple Negative Breast Neoplasms

Recent findings suggest that the inhibition of Aurora A (AURKA) kinase may offer a novel treatment strategy against metastatic cancers. In the current study, we determined the effects of AURKA inhibition by the small molecule inhibitor MLN8237 both as a monotherapy and in combination with the microtubule-targeting drug eribulin on different stages of metastasis in triple-negative breast cancer (TNBC) and defined the potential mechanism of its action. MLN8237 as a single agent and in combination with eribulin affected multiple steps in the metastatic process, including migration, attachment, and proliferation in distant organs, resulting in suppression of metastatic colonization and recurrence of cancer. Eribulin application induces accumulation of active AURKA in TNBC cells, providing foundation for the combination therapy. Mechanistically, AURKA inhibition induces cytotoxic autophagy via activation of the LC3B/p62 axis and inhibition of pAKT, leading to eradication of metastases, but has no effect on growth of mammary tumor. Combination of MLN8237 with eribulin leads to a synergistic increase in apoptosis in mammary tumors, as well as cytotoxic autophagy in metastases. These preclinical data provide a new understanding of the mechanisms by which MLN8237 mediates its antimetastatic effects and advocates for its combination with eribulin in future clinical trials for metastatic breast cancer and early-stage solid tumors. Mol Cancer Ther; 15(8); 1809-22. ©2016 AACR.

Topics: Animals; Aurora Kinase A; Autophagy; Azepines; Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Disease Models, Animal; Drug Synergism; Enzyme Activation; Female; Furans; Humans; Kaplan-Meier Estimate; Ketones; Male; Neoplasm Metastasis; Protein Kinase Inhibitors; Pyrimidines; Signal Transduction; Tumor Burden; Xenograft Model Antitumor Assays

Eribulin is a non-taxane, microtubule dynamics inhibitor that increases survival of patients with metastatic breast cancer. Although eribulin is well tolerated in patients with heavily pretreated disease, eribulin-induced liver dysfunction (EILD) can occur, resulting in treatment modification and subsequent poor disease control. We aimed to clarify the effect of EILD on patient survival.. The medical records of 157 metastatic breast cancer patients treated with eribulin between July 2011 and November 2013 at Cancer Institute Hospital were retrospectively analyzed. EILD was defined as 1) an increase in alanine aminotransferase or aspartate aminotransferase levels >3 times the upper limit of normal, and/or 2) initiation of a liver-supporting oral drug therapy such as ursodeoxycholic acid or glycyron. Fatty liver was defined as a decrease in the liver-to-spleen attenuation ratio to <0.9 on a computed tomography scan.. EILD occurred in 42 patients, including one patient for whom eribulin treatment was discontinued due to severe EILD. The patients who developed EILD had significantly higher body mass indices (BMIs) than those who did not develop EILD (24.5 vs. 21.5, respectively; P < 0.0001), with no difference in the dose intensity of eribulin between the two groups (P = 0.76). Interestingly, the patients with EILD exhibited significantly longer progression-free survival (PFS) and overall survival (OS) than those without EILD (P = 0.010 and P = 0.032, respectively). Similarly, among 80 patients without liver metastasis, 19 with EILD exhibited significantly longer PFS and OS than the others (P = 0.0012 and P = 0.044, respectively), and EILD was an independent prognostic factor of PFS (P = 0.0079) in multivariate analysis. During eribulin treatment, 18 patients developed fatty liver, 11 of whom developed EILD, with a median BMI of 26.7.. Although EILD and fatty liver occurred at a relatively high frequency in our study, most of the patients did not experience severe adverse effects. Surprisingly, the development of EILD was positively associated with patient survival, especially in patients without liver metastases. EILD may be a clinically useful predictive biomarker of survival, but further studies are needed to confirm these findings in another cohort of patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Body Mass Index; Breast Neoplasms; Chemical and Drug Induced Liver Injury; Disease-Free Survival; Female; Furans; Humans; Ketones; Liver Diseases; Middle Aged; Neoplasm Metastasis; Prognosis; Retrospective Studies; Survival Analysis; Tomography, X-Ray Computed; Treatment Outcome

There is no standard recommendation for metastatic breast cancer treatment (MBC) after two chemotherapy regimens. Eribulin (Halaven. A monocentric retrospective study was conducted at Institut Curie over 1 year (August 2012 to August 2013). Data from patient's medical records were extracted to estimate treatment and outcome patterns, and direct medical costs until the end of treatment were measured. Factors affecting cost variability were identified by multiple linear regressions and factors linked to OS by a multivariate Cox model.. We included 87 MBC patients. The median OS was 10.7 months (95%CI = 8.0-13.3). By multivariate Cox analysis, independent factors of poor prognosis were an Eastern Cooperative Oncology Group (ECOG) performance status of 3, a number of metastatic sites ≥ 4 and the need for hospitalization. Per-patient costs during whole treatment were €18,694 [CI 95%: 16,028-21,360], and €2581 [CI 95%: 2226-3038] per month. Eribulin administration contributed to 79% of per-patient costs.. Innovative and expensive drugs often appear to be the main cost drivers in cancer treatment, particularly for MBC. There is an urgent need to assess clinical practice benefits.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Cost-Benefit Analysis; Drug Costs; Female; France; Furans; Humans; Ketones; Linear Models; Liver Neoplasms; Lung Neoplasms; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Prognosis; Proportional Hazards Models; Retrospective Studies; Skin Neoplasms; Survival Rate

The purpose of treatment for patients with metastatic breast cancer is to maintain the patient's quality of life(QOL)with continued treatment for as long as possible.Eribulin was approved in April 2011 for the treatment of metastatic breast cancer, further increasing the selection of therapies available for the management of this disease.The current study presents a retrospective review of 31 patients who received eribulin in our hospital, and analyzes the factors related to the continuation and safety of its use.The median treatment continuation was 114 days(range, 8-281 days), and the treatment involved an average of 5 courses(range, 1-13 courses).There were no significant differences in the continuation of eribulin with regard to the number of previous chemotherapy regimens and modifications undergone by the patients.Neutropenia accounted for 80.6% of adverse eventsBGrade 3; however, the recovery was rapid.The rates of peripheral neuropathy and liver function failures were 12.9% and 6.5%, respectively. These results suggest that eribulin can be continued to be administered with the aim of maintaining QOL, and the therapy can be adjusted according to the patient's situation and the occurrence of adverse events by reducing the dose and treatment delays.

Topics: Adult; Aged; Breast Neoplasms; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Quality of Life; Retrospective Studies

There are many options in the treatment of heavily pretreated metastatic breast cancer however none of the therapeutic agents have shown promising improvement of survival with good toxicity profile. Eribulin is a novel nontaxane microtubule dynamics inhibitor. Two recent clinical trial showed that Eribulin improves progression-free and overall survival in this subset of patients. We report our experience with using Eribulin in five patients with metastatic breast cancer either in second or third-line setting, in our centre.

Topics: Antineoplastic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Malaysia; Neoplasm Metastasis; Treatment Outcome

This multicenter study describes the effectiveness of eribulin in current practice.. In total, 78 patients with advanced metastatic breast cancer, previously treated with two or more chemotherapy lines were enrolled.. The median duration of response and disease stability were 7.5 (5.4-9.5) and 8.9 (6.2-11.6) months, respectively, with a clinical benefit (CB) at 6 months in 41% of patients. CB in visceral and nonvisceral metastases were 72.7 and 88.9%, respectively. Eribulin was active also in brain metastases, with 47% CB. The activity was shown in all biological subtypes. Toxicities were manageable.. Our study confirms the effectiveness of eribulin mesylate in the treatment of patients with metastatic breast cancer and two or more lines of chemotherapy, in particular in the good disease control at the different metastatic sites.

Topics: Aged; Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Combined Modality Therapy; Disease Management; Disease Progression; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Prospective Studies; Retreatment; Treatment Outcome

No definitive cure is available for metastatic breast cancer and current therapies mainly focus on symptom control and minimization of adverse events to extend survival and maintain a good quality of life. Current treatment options include hormonal and chemotherapeutic agents which are characterized by different toxicity profiles and are selected based on patients' performance status and prior therapies. Eribulin is a microtubule dynamic inhibitor which acts by sequestering tubulin molecules into aggregates, thus preventing microtubule growth and causing apoptosis. Many studies show that heavily pretreated metastatic breast cancer patients benefit from eribulin treatment both in terms of efficacy and for the favorable toxicity profile. In the Phase III EMBRACE study, eribulin treatment resulted in a significant improvement in overall survival. We report here the case of a patient who experienced a time to progression of several months with eribulin after three lines of chemotherapy and two lines of hormonal therapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging

We report the case of a HER2(+) breast cancer patient, with early relapse, refractory to HER2-targeted therapy and treated with eribulin mesylate. The patient progressed during two different HER2 target therapies: trastuzumab as adjuvant/first-line treatment and lapatinib as second-line treatment. The patient underwent nine cycles of eribulin (1.23 mg/m(2) days 1-8 every 3 weeks). The therapy was well tolerated. Restaging with computed tomography after the second cycle of treatment demonstrated stable disease. After nine cycles of eribulin therapy the patient experienced disease progression and she died 6 months later. This case report provides further insights regarding the use of eribulin mesylate as third-line treatment in a HER2(+) breast cancer patient.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Fatal Outcome; Female; Furans; Humans; Ketones; Lapatinib; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Quinazolines; Receptor, ErbB-2; Retreatment; Trastuzumab

Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Moreover, many chemotherapeutic agents need to be interrupted due to toxicity. Here we report an extremely long duration of chemotherapy with eribulin (11 courses) in a taxane-pretreated metastatic breast cancer patient. Therapy was well tolerated with no worsening of pre-existing neuropathy, achieving excellent outcomes and a good quality of life. This report adds to the pool of knowledge regarding the use of this important new metastatic breast cancer chemotherapeutic agent.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Disease Progression; Female; Furans; Humans; Ketones; Neoplasm Metastasis; Retreatment; Taxoids; Treatment Outcome

In this short paper, we report our experience with eribulin mesylate in a heavily pretreated breast cancer patient with multiple bone metastases. The patient had been treated with doxorubicin, cyclophosphamide, methotrexate, fluorouracil, tamoxifen, letrozole, LH-RH analogs, fulvestrant, bevacizumab and paclitaxel and liposomal doxorubicin. In November 2013 treatment with eribulin ready to use solution (1.23 mg/m(2) days 1 and 8 of a 21-day cycle) was started and administered for a total of 14 courses. After six cycles of eribulin, evaluation with MRI showed a marked decrease in neoplastic involvement and replacement of osteolytic lesions with osteoblastic ones. No unexpected acute toxicity was observed. Although with all the limitations of any anecdotal report, our experience documents the efficacy and safety of eribulin in this difficult-to-treat patient who had been treated with multiple lines of chemotherapy.

Topics: Antineoplastic Agents; Breast Neoplasms; Combined Modality Therapy; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Retreatment; Treatment Outcome

EMA licensed eribulin mesylate in 2011 for women with advanced breast cancer already treated with at least two lines of chemotherapy, including anthracyclines and taxanes. Azienda Sanitaria Firenze experience is reported to assess the efficacy and safety of eribulin in the real-life setting.. Eribulin was infused as per indication. All women treated in the last 2 years were reviewed.. A total of 27 women received eribulin. All but one was pretreated with anthracyclines, 97% with taxanes and 87% with capecitabine. Median age was 63 years (range: 27-80). A median of four cycles of eribulin were infused (range: 2-10). Overall response rate was 30% with a 45% of clinical benefit (response plus stable disease for at least 24 weeks). Toxicities have been as expected. Severe toxicities were rare, with one patient experiencing sepsis and 18% developing grade 3 asthenia.. Eribulin maintains its activity out of clinical trials, without unexpected toxicities.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Retrospective Studies; Treatment Outcome; Young Adult

The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow-disseminated tumor cells (DTC)-negative patients at high risk for metastasis and death. The protein epitope mimetic (PEM) POL5551, a novel CXCR4 antagonist, inhibited binding of SDF-1 to CXCR4, had no direct effects on tumor cell viability, but reduced migration of breast cancer cells in vitro. In two orthotopic models of triple-negative breast cancer, POL5551 had little inhibitory effect on primary tumor growth, but significantly reduced distant metastasis. When combined with eribulin, a chemotherapeutic microtubule inhibitor, POL5551 additively reduced metastasis and prolonged survival in mice after resection of the primary tumor compared with single-agent eribulin. Hypothesizing that POL5551 may mobilize tumor cells from their microenvironment and sensitize them to chemotherapy, we used a "chemotherapy framing" dosing strategy. When administered shortly before and after eribulin treatment, three doses of POL5551 with eribulin reduced bone and liver tumor burden more effectively than chemotherapy alone. These data suggest that sequenced administration of CXCR4 antagonists with cytotoxic chemotherapy synergize to reduce distant metastases.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Biomimetic Materials; Cell Line, Tumor; Cell Movement; Cell Survival; Chemokine CXCL12; Epitopes; Furans; Humans; Ketones; Mice, Inbred BALB C; Mice, Inbred NOD; Mice, SCID; Mice, Transgenic; Neoplasm Metastasis; Protein Binding; Proteins; Receptors, CXCR4; Signal Transduction; Survival Analysis; Triple Negative Breast Neoplasms; Tumor Burden; Xenograft Model Antitumor Assays

Our retrospective, international study aimed at evaluating the activity and safety of eribulin mesylate (EM) in pretreated metastatic breast cancer (MBC) in a routine clinical setting.. Patients treated with EM for a locally advanced or MBC between March 2011 and January 2014 were included in the study. Clinical and biological assessment of toxicity was performed at each visit. Tumour response was assessed every 3 cycles of treatment. A database was created to collect clinical, pathological and treatment data.. Two hundred and fifty-eight patients were included in the study. Median age was 59 years old. Tumours were Hormone Receptor (HR)-positive (73.3 %) HER2-positive (10.2 %), and triple negative (TN, 22.5 %). 86.4 % of the patients presented with visceral metastases, mainly in the liver (67.4 %). Median previous metastatic chemotherapies number was 4 [1-9]. Previous treatments included anthracyclines and/or taxanes (100 %) and capecitabine (90.7 %). Median number of EM cycles was 5 [1-19]. The relative dose intensity was 0.917. At the time of analysis (median follow-up of 13.9 months), 42.3 % of the patients were still alive. The objective response rate was 25.2 % (95 %CI: 20-31) with a 36.1 % clinical benefit rate (CBR). Median time to progression (TTP) and overall survival were 3.97 (95 %CI: 3.25-4.3) and 11.2 (95 %CI: 9.3-12.1) months, respectively. One- and 2-year survival rates were 45.5 and 8.5 %, respectively. In multivariate analysis, HER2 positivity (HR = 0.29), the presence of lung metastases (HR = 2.49) and primary taxanes resistance (HR = 2.36) were the only three independent CBR predictive factors, while HR positivity (HR = 0.67), the presence of lung metastases (HR = 1.52) and primary taxanes resistance (HR = 1.50) were the only three TTP independent prognostic factors. Treatment was globally well tolerated. Most common grade 3-4 toxicities were neutropenia (20.9 %), peripheral neuropathy (3.9 %), anaemia (1.6 %), liver dysfunction (0.8 %) and thrombocytopenia (0.4 %). Thirteen patients (5 %) developed febrile neutropenia.. EM is an effective new option in heavily pretreated MBC, with a favourable efficacy/safety ratio in a clinical practice setting. Our results comfort the use of this new molecule and pledge for the evaluation of EM-trastuzumab combination in this setting. Tumour biology, primary taxanes sensitivity and metastatic sites could represent useful predictive and prognostic factors.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Drug Resistance, Neoplasm; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Retrospective Studies; Taxoids; Treatment Outcome; Young Adult

The aim of this study is to report on the activity and safety of eribulin mesylate in a representative number of pretreated metastatic breast cancer (MBC) patients in current practice. Eribulin mesylate, a new microtubule inhibitor, is approved as monotherapy for the treatment of patients with locally advanced breast cancer or MBC who have progressed after at least two chemotherapeutic regimens for advanced disease.. From February to October 2012, 27 MBC patients, previously treated with anthracyclines and taxanes, were treated with 1.4 mg/m(2) intravenous infusion of eribulin mesylate at a community hospital.. Eight (30%) patients achieved partial response, one achieved complete response and three achieved stable disease. Median duration of response was 2.5 months (95% CI: 1.6-5.7; range: 1.3-5.7). Median overall survival was 8 months (95% CI: 6.1-9.7; range: 0.6-9.9). Reported adverse events were grade 1-2 asthenia (83%), peripheral sensory neuropathy (48%), nausea (37%) and neutropenia (30%).. Our retrospective analysis of a clinical practice experience supports the evidence that eribulin mesylate has clinical activity and provides acceptable benefit to heavily pretreated MBC.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Female; Furans; Hospitals, Community; Humans; Italy; Ketones; Middle Aged; Neoplasm Metastasis; Retreatment; Treatment Outcome

Eribulin mesilate (eribulin), a non-taxane microtubule dynamics inhibitor, has shown trends towards greater overall survival (OS) compared with progression-free survival in late-stage metastatic breast cancer patients in the clinic. This finding suggests that eribulin may have additional, previously unrecognised antitumour mechanisms beyond its established antimitotic activity. To investigate this possibility, eribulin's effects on the balance between epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) in human breast cancer cells were investigated.. Triple negative breast cancer (TNBC) cells, which are oestrogen receptor (ER-)/progesterone receptor (PR-)/human epithelial growth receptor 2 (HER2-) and have a mesenchymal phenotype, were treated with eribulin for 7 days, followed by measurement of EMT-related gene and protein expression changes in the surviving cells by quantitative real-time PCR (qPCR) and immunoblot, respectively. In addition, proliferation, migration, and invasion assays were also conducted in eribulin-treated cells. To investigate the effects of eribulin on TGF-β/Smad signalling, the phosphorylation status of Smad proteins was analysed. In vivo, the EMT/MET status of TNBC xenografts in mice treated with eribulin was examined by qPCR, immunoblot, and immunohistochemical analysis. Finally, an experimental lung metastasis model was utilised to gauge the metastatic activity of eribulin-treated TNBC in the in vivo setting.. Treatment of TNBC cells with eribulin in vitro led to morphological changes consistent with transition from a mesenchymal to an epithelial phenotype. Expression analyses of EMT markers showed that eribulin treatment led to decreased expression of several mesenchymal marker genes, together with increased expression of several epithelial markers. In the TGF-β induced EMT model, eribulin treatment reversed EMT, coincident with inhibition of Smad2 and Smad3 phosphorylation. Consistent with these changes, TNBC cells treated with eribulin for 7 days showed decreased capacity for in vitro migration and invasiveness. In in vivo xenograft models, eribulin treatment reversed EMT and induced MET as assessed by qPCR, immunoblot, and immunohistochemical analyses of epithelial and mesenchymal marker proteins. Finally, surviving TNBC cells pretreated in vitro with eribulin for 7 days led to decreased numbers of lung metastasis when assessed in an in vivo experimental metastasis model.. Eribulin exerted significant effects on EMT/MET-related pathway components in human breast cancer cells in vitro and in vivo, consistent with a phenotypic switch from mesenchymal to epithelial states, and corresponding to observed decreases in migration and invasiveness in vitro as well as experimental metastasis in vivo. These preclinical findings may provide a plausible scientific basis for clinical observations of prolonged OS by suppression of further spread of metastasis in breast cancer patients treated with eribulin.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Disease-Free Survival; Epithelial-Mesenchymal Transition; Female; Furans; Gene Expression; Humans; Ketones; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Metastasis; Phenotype; Triple Negative Breast Neoplasms; Xenograft Model Antitumor Assays

In the EMBRACE trial, eribulin was reported to significantly increase overall survival compared to treatment of the physician 's choice when given to patients with recurrent or metastatic breast cancer who had received prior treatment, including an anthracycline and a taxane. In April 2011, eribulin was approved in Japan for the treatment of inoperable or recurrent breast cancer. In this article, we report on the efficacy and safety of eribulin in cases we encountered. Twenty patients with advanced and recurrent breast cancer were administered eribulin in our hospital during the period from August 2011 to December 2012. The median age was 62 years(range, 42-76 years); 16 patients had the estrogen receptor(ER)(+)/human epidermal growth factor receptor 2(HER2)(-)subtype, whereas 4 patients had the triple-negative subtype. Following recurrence, the median number of chemotherapy regimens was 3(range, 0-5). Regarding the antitumor effects of eribulin, no cases showed complete response(CR), 5 cases showed partial response(PR), and 10 cases showed stable disease(SD); therefore, the response rate(CR+PR)was 25% and the clinical benefit rate(CR+PR+B6-month SD)was 35%. Median progression free survival was 146 days, and median overall survival was 482 days. In terms of adverse events(AEs), observed cases of hematotoxicity were of neutropenia(75%), leucopenia(75%), and anemia(80%). Cases of Grade 3 hematotoxicity or higher were of neutropenia(40%), leucopenia(20%), and febrile neutropenia(1 case, 5%). The observed non-hematotoxic AEs were peripheral neuropathy(30%)and general malaise(35%), although none were of Grade 3 or higher. The therapeutic efficacy of eribulin in the present study was relatively better than that in previous reports(EMBRACE trial, Japan Domestic 221 trial). The frequency of Grade 3 or higher AEs was low, and the drug was well tolerated. We believe that eribulin is a novel drug that provides therapeutic efficacy while maintaining quality of life(QOL).

Topics: Adult; Aged; Breast Neoplasms; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Recurrence; Treatment Outcome

Clinical outcomes, including adverse events, in 52 advanced breast cancer patients treated with eribulin chemotherapy after taxane treatment (TX) were analyzed to confirm the effectiveness and safety of this treatment.The objective response rate (ORR) in patients was 34.6% (TX group 31.6%, non-TX group 36.4%). There were no significant differences in overall survival, time to treatment failure, or progression-free between three TX and non-TX groups. Further, adverse events did not differ between groups expression of neutropenia of Grade 3 or more. On the other hand, the number of patients with sensory peripheral neuropathy of Grade 1 or more was significantly more in the TX group than in the non-TX group. Eribulin chemotherapy was effective for the treatment of advanced breast cancer regardless of a history of taxane treatment.In addition, sensory peripheral neuropathy is a possible complication that can occur in advanced breast cancer patients treated with eribulin chemotherapy with taxane treatment history.

Topics: Breast Neoplasms; Bridged-Ring Compounds; Drug Resistance, Neoplasm; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Peripheral Nervous System Diseases; Taxoids

Eribulin mesylate, a novel microtubule inhibitor with a unique mechanism of action, was approved in Japan in April 2011 for the treatment of metastatic breast cancer patients who had been administered at least two prior chemotherapeutic agents. Here, we present a retrospective review of data from 27 patients who received eribulin monotherapy in our hospital. The overall response rate and clinical benefit rate were 25. 9% and 29. 6%, respectively, and the median progression-free survival was 9. 9 weeks(95% CI: 3. 5-16. 2 weeks). The toxicities of treatment were tolerable and manageable; responses were lower in patients who were triple negative subtype, and higher in patients who had responded to prior taxane treatment. The relative dose intensity of our data indicates that appropriate modification of dose and schedule may be an important part of eribulin monotherapy.

Topics: Adult; Aged; Breast Neoplasms; Clinical Trials as Topic; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Retrospective Studies; Treatment Outcome

This observational study evaluated the behavior and outcome of cutaneous breast cancer metastasis treated with eribulin.. From November 2012 to January 2013, oncologists completed a database with patient, tumor and treatment characteristics from 14 Italian cancer centers. Skin lesions were assessed by Response Evaluation Criteria In Solid Tumors and cutaneous symptoms by present/absent criteria.. A total of 23 metastatic breast cancer patients with skin metastasis who were treated with eribulin were analyzed. After treatment, 43% of patients exhibited a partial response, 35% stable disease and 22% progressive disease. Regarding only the skin response, 26% obtained a complete response, 22% a partial response, 39% stable disease and 13% progressive disease. We found an improvement in symptoms, infiltration and ulceration. With a median follow-up of 6 months, median progression-free survival was 4.3 months and median overall survival was 9.1 months.. The response rate of skin metastasis to eribulin treatment was coherent with systemic responses. The good clinical response in most patients reflected symptom improvement.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Disease-Free Survival; Female; Furans; Humans; Ketones; Middle Aged; Neoplasm Metastasis; Skin Neoplasms

Eribulin was FDA approved in 2012 as a treatment for patients with MBC who have previously received at least two prior chemotherapy regimens. The aim of this analysis was to assess the cost effectiveness of eribulin versus the three most commonly utilized drugs (TPC) in the EMBRACE trial: vinorelbine, gemcitabine, and capecitabine (X); and to other branded FDA approved drugs: ixabepilone (I), liposomal-doxorubicin (D), and nab-paclitaxel. We created a decision-analytical and a Markov model using clinical data from the EMBRACE trial. Health utilities were derived from the published literature. Costs for drug acquisition, physician visits, and laboratory tests were obtained from Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2012 USD. Life-years saved (LY), quality-adjusted life years (QALY), and incremental cost effectiveness ratio (ICER) were calculated. Eribulin added 0.208 LY and 0.119 QALY with an incremental cost over TPC of $25,458, and therefore an ICER of $213,742 per QALY. The main drivers of the model were drug cost, PFS, OS, and health utility values. The results of the model were robust in sensitivity analyses. Relative to I, D, A, and X, the ICER for eribulin was $76,823, $109,283, $129,773, and $167,267, respectively. Even with a more contemporary willingness-to-pay threshold of approximately $120,000 per QALY, eribulin was not found to be cost effective in the treatment of MBC relative to TPC; relative to some more expensive branded drugs, eribulin appears to be cost effective.

Topics: Albumins; Antineoplastic Agents; Breast Neoplasms; Capecitabine; Cost-Benefit Analysis; Decision Making, Computer-Assisted; Deoxycytidine; Disease-Free Survival; Doxorubicin; Drug Resistance, Neoplasm; Epothilones; Female; Fluorouracil; Furans; Humans; Ketones; Markov Chains; Neoplasm Metastasis; Paclitaxel; Quality of Life; Treatment Outcome

This work describes the considerations that led to the approval by the U.S. Food and Drug Administration (FDA), on November 15, 2010, of eribulin mesylate (Halaven; Eisai, Inc.) for the treatment of patients with refractory metastatic breast cancer. The FDA review focused primarily on the results of a single randomized, open-label, multicenter trial of 762 patients with refractory locally advanced or metastatic breast cancer. The patients were randomized to receive eribulin or any single-agent treatment of the physician's choice, selected prior to randomization. The FDA's approval of eribulin mesylate was based on demonstration of a statistically significant prolongation of overall survival (OS) in patients who had been randomized to receive eribulin. The median OS was 13.1 months in the eribulin arm compared with 10.6 months in the control arm [HR 0.81 (95% CI, 0.66-0.99); P = 0.041]. Treatment with eribulin did not show a statistically significant treatment effect [HR 0.87 (95% CI, 0.71-1.05)] on progression-free survival as determined by independent review. This approval highlights the appropriate use of an innovative trial design and shows that improvement in OS is an achievable endpoint in the setting of advanced breast cancer. On the basis of the different conclusions arising from the OS and progression-free survival results, investigators should consider using OS as a primary endpoint in clinical trials for refractory breast cancer.

Topics: Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Drug Approval; Female; Furans; Humans; Ketones; Multicenter Studies as Topic; Neoplasm Metastasis; Randomized Controlled Trials as Topic; Retreatment; United States; United States Food and Drug Administration

There is no standard third-line chemotherapy treatment option for patients with metastatic breast cancer who have received an anthracycline and/or a taxane. A recent Phase III randomized controlled trial compared a new agent, eribulin mesylate with physician's treatment of choice in heavily pretreated patients with metastatic breast cancer, and a survival advantage was observed. Eribulin is a non-taxane microtubule dynamics inhibitor, approved by the US Food and Drug Administration (FDA) in November 2010 for use in patients who previously received at least two prior lines of chemotherapy for metastatic breast cancer.. The mechanism of action, pharmacokinetics and the efficacy and safety data from preclinical and clinical trials of this new agent are presented in this paper.. Phase II and a recent Phase III trial indicate that eribulin is well tolerated with a predictable safety profile. The most frequent adverse events observed in patients receiving eribulin were asthenia/fatigue, neutropenia, alopecia, peripheral neuropathy and nausea. It represents a new treatment option in the setting of anthracycline and taxane-refractory metastatic breast cancer.

Topics: Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Female; Furans; Humans; Ketones; Neoplasm Metastasis

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Cell Proliferation; Female; Furans; Humans; Ketones; Microtubules; Neoplasm Metastasis; Tubulin Modulators

Topics: Antineoplastic Agents; Breast Neoplasms; Drug Approval; Ethers, Cyclic; Female; Furans; Humans; Ketones; Macrolides; Mesylates; Microtubules; Neoplasm Metastasis

Topics: Antineoplastic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Neoplasm Metastasis; Survival Rate

Approximately 30% of patients with breast cancer will develop metastatic breast disease. Metastatic breast cancer is considered an incurable disease, with complete remission rarely achieved after treatment. The goal of treatment for metastatic breast cancer patients is to increase overall survival time and delay disease progression while ameliorating symptoms and improving or maintaining quality of life. Single-agent therapeutic regimens are appropriate for most metastatic breast cancer patients. Patients with the luminal A subtype of breast cancer, which is more indolent in nature and tends to be more sensitive to treatment in general, often respond well to single-agent therapy. Several chemotherapy regimens are recommended for the treatment of metastatic breast cancer. Compared with single-agent regimens, these combination regimens often produce a greater improvement in the rate of objective response as well as a prolongation of progression-free survival. There is little evidence, however, of improvement in overall survival. Combination chemotherapy regimens are often associated with a greater degree of toxicity depending on schedules and doses used. The use of bevacizumab in metastatic breast cancer is currently a topic of controversy. It is hoped that forthcoming trial data will enable the identification of a group of patients, based on tumor biology, who could benefit from bevacizumab-based therapy.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Density Conservation Agents; Breast Neoplasms; Capecitabine; Deoxycytidine; Female; Fluorouracil; Furans; Humans; Ketones; Neoplasm Metastasis; Prognosis; Protein Kinase Inhibitors; Receptor, ErbB-2; Taxoids; Tubulin Modulators; Vascular Endothelial Growth Factor A

Approximately 30% of patients with breast cancer will develop metastatic breast disease. Metastatic breast cancer is considered an incurable disease, with complete remission rarely achieved after treatment. The goal of treatment for metastatic breast cancer patients is to increase overall survival time and delay disease progression while ameliorating symptoms and improving or maintaining quality of life. Single-agent therapeutic regimens are appropriate for most metastatic breast cancer patients. Patients with the luminal A subtype of breast cancer, which is more indolent in nature and tends to be more sensitive to treatment in general, often respond well to single-agent therapy. Several chemotherapy regimens are recommended for the treatment of metastatic breast cancer. Compared with single-agent regimens, these combination regimens often produce a greater improvement in the rate of objective response as well as a prolongation of progression-free survival. There is little evidence, however, of improvement in overall survival. Combination chemotherapy regimens are often associated with a greater degree of toxicity depending on schedules and doses used. The use of bevacizumab in metastatic breast cancer is currently a topic of controversy. It is hoped that forthcoming trial data will enable the identification of a group of patients, based on tumor biology, who could benefit from bevacizumab-based therapy.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast; Breast Neoplasms; Capecitabine; Deoxycytidine; Female; Fluorouracil; Furans; Humans; Ketones; Neoplasm Metastasis; Receptor, ErbB-2; Taxoids; Tubulin Modulators