er-086526 and taxane

Metastatic breast cancer is currently incurable and the goals of therapy focus on prolonging survival and maintaining quality of life by controlling symptoms and minimizing toxicity. Treatments for metastatic breast cancer include chemotherapeutic agents from various classes, such as taxanes, vinca alkaloids, anthracyclines and antimetabolites. This review provides an overview of chemotherapeutic agents for the treatment of metastatic breast cancer patients previously treated with anthracyclines and taxanes, focusing on a clinical evaluation of eribulin, the most recently approved agent for the treatment of metastatic breast cancer. Eribulin is a synthetic derivative of halichondrin B, a tumour growth inhibitor found in marine sponges, which prevents microtubule growth and sequesters the tubulin molecules into unusual aggregates, initiating apoptosis. Studies of eribulin have shown that the drug is effective in the treatment of previously treated metastatic breast cancer, and has an acceptable toxicity profile. Importantly, in the phase III EMBRACE study, eribulin treatment resulted in a survival advantage, a difficult endpoint to achieve with a single chemotherapeutic agent. An additional phase III study showed that eribulin has similar efficacy to capecitabine in women treated with no more than three prior therapies. Furthermore, pre-specified exploratory analyses suggest that particular patient subgroups may have greater therapeutic benefit with eribulin and may warrant further study to explore the potential mechanisms.

Topics: Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Clinical Trials, Phase III as Topic; Female; Furans; Humans; Ketones; Taxoids

The sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC.. In this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection. The primary endpoint was the clinical response rate. Eligible patients were women aged 20 years or older, with histologically confirmed invasive breast cancer, clinical Stage IIIA (T2-3 and N2 only), Stage IIIB, and Stage IIIC, HER2-negative.. A preplanned interim analysis aimed to validate the trial assumptions was conducted after treatment of 20 patients and demonstrated that clinical progressive disease rates in the E phase were significantly higher (30%) than assumed. Therefore, the Independent Data Monitoring Committee recommended stopping the study. Finally, 53 patients were enrolled, and 26 patients received the A/T/E-regimen. The overall observed clinical response rate (RR) was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. Thirty percent (8/26) of patients had PD in the E phase, 6 of whom had achieved cCR/PR in the AT phase. Reported grade ≥ 3 AEs related to E were neutropenia (42%), white blood cell count decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%).. Sequential administration of eribulin after the A/T-regimen provided no additional effect for LABC patients. Future research should continue to focus on identifying specific molecular biomarkers that can improve response rates.

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Female; Furans; Humans; Ketones; Neoadjuvant Therapy; Prospective Studies; Receptor, ErbB-2; Taxoids; Treatment Outcome

Women with residual invasive breast cancer at the primary site or axillary lymph nodes following neoadjuvant chemotherapy have a high risk of recurrence. Eribulin improves survival in patients with metastatic breast cancer who progress after anthracycline and taxane therapy. This phase 2 trial assessed the efficacy of postoperative eribulin in breast cancer patients who did not achieve a pCR following standard neoadjuvant chemotherapy.. Women with localized breast cancer who had residual invasive cancer following ≥ 4 cycles of standard anthracycline and/or taxane-containing neoadjuvant chemotherapy received adjuvant eribulin treatment. HER2-positive patients also received trastuzumab for 1 year. Adjuvant hormonal therapy and locoregional radiotherapy were administered as per institutional guidelines. Primary endpoint was the 2-year DFS rate. Three patient cohorts were analyzed: TNBC (Cohort A), HR+/HER2- (Cohort B), and HER2+ (Cohort C).. One hundred twenty-six patients (Cohort A-53, Cohort B-42, and Cohort C-31) were enrolled. Neoadjuvant chemotherapy included a taxane and an anthracycline in 70%. Eribulin was well tolerated; 84% of patients received the planned 6 cycles. After a median follow-up of 28 months, the 24-month DFS rates were 56% (95% CI 42, 69), 83% (95% CI 67, 91), and 73% (95% CI 53, 86) for Cohorts A, B, and C, respectively. The most common grade 3/4 treatment-related adverse events were neutropenia (26%), leukopenia (13%), and neuropathy (7%).. Administration of adjuvant eribulin after neoadjuvant chemotherapy was feasible and well tolerated. The 24-month DFS rate did not reach the study target levels in any of the cohorts and was similar to DFS previously described in these cohorts following neoadjuvant chemotherapy alone.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Bridged-Ring Compounds; Chemotherapy, Adjuvant; Cohort Studies; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Furans; Humans; Ketones; Middle Aged; Neoadjuvant Therapy; Non-Randomized Controlled Trials as Topic; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Survival Rate; Taxoids; Trastuzumab

Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy.. Patients with primary triple negative breast cancer ≥2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study.. In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2-5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR.. Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial-mesenchymal transition, claims for further investigation.. EU Clinical Trial Register, EudraCT number 2012-004956-12.

Topics: Adult; Anthracyclines; Bridged-Ring Compounds; Female; Furans; Humans; Ketones; Neoadjuvant Therapy; Taxoids; Treatment Outcome; Triple Negative Breast Neoplasms

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

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

Eribulin mesylate (E7389) is an analog of halichondrin B with a unique mechanism of microtubule binding. The activity and toxicity of eribulin were assessed in patients with advanced non-small cell lung cancer (NSCLC) previously treated with a taxane.. An open-label phase II study included patients with NSCLC previously treated with platinum and taxane-based therapy, with up to two prior cytotoxic regimens, given for metastatic disease or as adjuvant therapy. Patients were stratified by taxane-sensitivity: taxane-sensitive (TS, progression >90 days after taxane) or taxane-resistant (TR, progression ≤90 days after taxane). Patients received an intravenous infusion of eribulin at 1.4 mg/m on days 1 and 8 every 21 days. The primary end point was objective response rate and secondary end points included progression-free survival and overall survival.. Sixty-six patients were accrued. The objective response rate was 5% with a median duration of response of 7.8 months. In the TS arm, 3 of 45 patients (7%) achieved a partial response and another 11 of 45 (24%) achieved stable disease for at least 3 months, whereas in the TR arm, no patients achieved a partial response and 4 of 21 (19%) achieved stable disease for at least 3 months. Median progression-free survival was 2.9 months in the TS subgroup and 1.2 months in the TR subgroup. The median overall survival was 12.6 months in the TS subgroup and 8.9 months in the TR subgroup. Toxicities were primarily hematologic; only two patients developed grade 3 neuropathy.. Eribulin mesylate is well tolerated and demonstrates activity in pretreated, TS NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Ethers, Cyclic; Female; Follow-Up Studies; Furans; Humans; Ketones; Lung Neoplasms; Macrolides; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Platinum; Salvage Therapy; Survival Rate; Taxoids; Treatment Outcome

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

Treatments for endocrine-refractory or triple-negative metastatic breast cancer (mBC) are modestly effective at prolonging life and improving quality of life but can be extremely expensive. Given these tradeoffs in quality of life and cost, the optimal choice of treatment sequencing is unclear. Cost-effectiveness analysis can explicitly quantify such tradeoffs, enabling more informed decision making. Our objective was to estimate the societal cost-effectiveness of different therapeutic alternatives in the first- to third-line sequences of single-agent chemotherapy regimens among patients with endocrine-refractory or triple-negative mBC.. Using three dynamic microsimulation models of 10,000 patients each, three cohorts were simulated, based upon prior chemotherapy exposure: (1) unexposed to either taxane or anthracycline, (2) taxane- and anthracycline-exposed, and (3) taxane-exposed/anthracycline-naive. We focused on the following single-agent chemotherapy regimens as reasonable and commonly used options in the first three lines of therapy for each cohort, based upon feedback from oncologists treating endocrine-refractory or triple-negative mBC: (1) for taxane- and anthracycline-unexposed patients, paclitaxel, capecitabine (CAPE), or pegylated liposomal doxorubicin; (2) for taxane- and anthracycline-exposed patients, Eribulin, CAPE, or carboplatin; and (3) for taxane-exposed/anthracycline-naive patients, pegylated liposomal doxorubicin, CAPE, or Eribulin.. In each cohort, accumulated quality-adjusted life-years were similar between regimens, but total societal costs varied considerably. Sequences beginning first-line treatment with paclitaxel, carboplatin, and CAPE, respectively, for cohorts 1, 2, and 3, had lower costs and similar or slightly better outcomes compared with alternative options.. In this setting where multiple single-agent chemotherapy options are recommended by clinical guidelines and share similar survival and adverse event trajectories, treatment sequencing approaches that minimize costs early may improve the value of care.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Carboplatin; Cost-Benefit Analysis; Doxorubicin; Female; Humans; Paclitaxel; Quality of Life; Taxoids

Cutaneous angiosarcoma (CAS) is a rare and highly aggressive type of vascular tumor. Although chemoradiotherapy with taxanes is recognized as a first-line therapy for CAS, second-line therapy for CAS remains controversial. From the above findings, the efficacy and safety profiles of taxane-switch (change paclitaxel to docetaxel or vise), eribulin methylate, and pazopanib regimens in second-line chemotherapy were evaluated retrospectively in 50 Japanese taxane-resistant CAS patients. Although there was no significant difference in progression-free survival (P = 0.3528) among the regimens, the incidence of all adverse events (AEs) (P = 0.0386), as well as severe G3 or more AEs (P = 0.0477) was significantly higher in the eribulin methylate group and pazopanib group than in the taxane-switch group. The present data suggest that switching to another taxane should be considered for the treatment of taxane-resistant CAS in second-line therapy based on the safety profiles.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; East Asian People; Female; Hemangiosarcoma; Humans; Paclitaxel; Retrospective Studies; Skin Neoplasms; Taxoids

Taxanes are the current first-line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. However, no effective second-line therapy for such patients has been established.. We designed a single-arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m. We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference.. ERB showed a promising RR and is a potential candidate for second-line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients. What is already known about this topic? Taxanes are the current first-line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. No effective therapy for taxane-resistant CAS has been established thus far. Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single-arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression-free survival were 8·6 and 3·0 months, respectively. Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively. Although 16 grade 3/4 severe adverse events occurred, all patients recovered. Eribulin showed a promising response rate and is a potential candidate for second-line treatment in CAS after taxane treatment. Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797-798.

Topics: Aged; Breast Neoplasms; Bridged-Ring Compounds; Furans; Hemangiosarcoma; Humans; Ketones; Taxoids; Treatment Outcome

This multicenter, observational study aimed to investigate the survival benefit of eribulin as well as that of taxane-based regimens in Japanese patients with metastatic breast cancer (MBC) in a real-world setting.. This study enrolled women with MBC who received eribulin or taxane-based regimens with or without bevacizumab in routine clinical practice from July 2011 to March 2014. Patients were followed until September 2015. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), post-progression survival (PPS) and adverse events. Efficacy findings were adjusted according to demographics.. In total, 216 patients receiving eribulin monotherapy (n = 101), taxane monotherapy (n = 73) or taxane plus bevacizumab (n = 42) were followed for a median time of 15.4 months. Median OS, PFS and PPS were 22.3, 8.1 and 14 months in the eribulin monotherapy group; 13.2, 3.6 and 7.6 months in the taxane monotherapy group; and 12.9, 5.7 and 6.3 months, in the taxane plus bevacizumab group, respectively. The incidence of neutropenia was 67.3, 41.1 and 16.7%, and the incidence of grade 4 neutropenia was 1.0, 8.2 and 7.1% in the eribulin monotherapy, taxane monotherapy and taxane plus bevacizumab groups, respectively. One patient (1.0%) discontinued eribulin and 18 patients (15.7%) discontinued taxane-based regimens because of adverse events.. In Japanese MBC patients in a real-world setting, eribulin showed a survival benefit and tolerability similar to that in previous reports.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Bridged-Ring Compounds; Female; Furans; Humans; Ketones; Middle Aged; Taxoids; Treatment Outcome

Metastatic breast cancer (MBC) rest an incurably disease associated with bad prognosis and a median overall survival of 23-31 months. There are several treatment options including chemotherapy and sometimes endocrine therapy. Currently, there is no standard treatment for patients with MBC who have already benefited from anthracyclines and taxanes therapy. Many drugs like capecitabine, eribulin, gemcitabine, vinorelbin and liposomal doxorubicin are conventionally used as monotherapy. One important complication from MBC is life threating visceral crisis that needs a fast-effective treatment.. We report here a case of an evolution of metastatic breast cancer with lymphangitic carcinomatosis after taxane based chemotherapy and endocrine therapy. This 37-year-old woman was referred to our hospital with complaints of dyspnea and dry cough. There was clinical concern for visceral crisis and a chemotherapy with eribulin was initiated. Pulmonary lymphangitic carcinomatosis disappeared and the patient achieved a good partial response.. We reported a case of rapid, positive treatment response using eribulin on metastatic breast cancer with visceral crisis and we could quoted others. Therefore, eribulin may be an appropriate chemotherapeutic option in instances requiring rapid symptom control.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma; Female; Furans; Humans; Ketones; Lung Neoplasms; Taxoids

Recent clinical, randomized and observational studies showed that eribulin, an analogous of Halichondrin B, was beneficial and well-tolerated in heavily pretreated metastatic breast cancer patients. Here, we aim to evaluate the effectiveness and safety of eribulin in taxane-refractory metastatic breast cancer patients.. In this subanalysis of the ESEMPIO study database, we selected 91 subjects with well-defined taxane refractoriness and complete data available.. 41 patients (45.2%) showed clinical benefit; one complete response (2.2%) and 16 partial responses (17.6%) were observed. Median progression-free survival and median overall survival were 3.1 and 11.6 months, respectively. The most experienced adverse event was asthenia/fatigue (58%), followed by neutropenia (30%). The treatment-related toxicity led to eribulin-dose reduction in 19 patients and suspension in nine.. This study shows that eribulin is effective and well tolerated also in taxane-refractory patients in clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Furans; Humans; Ketones; Middle Aged; Multicenter Studies as Topic; Retreatment; Taxoids; Treatment Outcome

We experienced 2 cases in which eribulin mesylate was effective for taxane-resistant advanced breast cancer. Case 1: A 65- year-old woman was diagnosed with advanced breast cancer(T4cN2aM0, stage III B)and treated with chemotherapy(nabpaclitaxel). Bone metastasis was observed; then, she sequentially received epirubicin and cyclophosphamide, nab-paclitaxel, and bevacizumab and paclitaxel. However, lung metastases appeared, and we changed the regimen to eribulin mesylate. We administered 11 courses of eribulin mesylate before bone marrow metastasis appeared. Eribulin mesylate was effective for more than 1 year. Case 2: A 77-year-old woman was diagnosed with advanced breast cancer(T4bN3cM1, stage IV), and liver and pleural metastasis were observed during an examination at the first visit. Four courses of nab-paclitaxel were administered, but because of the increase in pleural effusion, we changed the regimen to eribulin mesylate. Thirteen courses of eribulin mesylate were administered before the disease progressed. The progression-free survival was 9.53 months. Through the 2 cases in which eribulin mesylate was effective for taxane-resistant advanced breast cancer, the effect of eribulin mesylate compared to taxane was clinically inferred.

Topics: Aged; Breast Neoplasms; Bridged-Ring Compounds; Drug Resistance, Neoplasm; Female; Furans; Humans; Ketones; Neoplasm Staging; Taxoids; Treatment Outcome

This retrospective observational study contains advanced or metastatic breast cancer female patients who pretreated with anthracycline and/or taxane received eribulin(ERI)mesylate. The primary endpoint was the progressionfree survival(PFS)and secondary endopoints were objective response rate(ORR), clinical benefit rate(CBR), overall survival (OS), and post-progression survival(PPS).. A total of 32 patients underwent chemotherapy cycles(median 3; range 1-9 cycles). The ORR was 15.6% and the CBR was 31.3%. The median PFS, OS and PPS were 2.9 months, 8.5 months, 5.6 months respectively. The OS, PPS for relative dose intensity(RDI)<85% and RDI≥85% were 7.2 months, 3.4 months and 14.5 months, 11.4 months, respectively(p=0.005, 0.004). In multivariate analysis for OS and PPS, the visceral disease, total dose of ERI and RDI correlated with OS and PPS. The most frequent treatment-related Grade 3/4 adverse events was neutropenia( 56%). No Grade 3 and 4 peripheral sensory neuropathy was occurred.. ERI exhibited efficacy and tolera- bility in patients with heavily pretreated A/MBC. The total dose and RDI of ERI would induce favorable effect for prognosis.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Disease Progression; Drug Resistance, Neoplasm; Furans; Humans; Ketones; Middle Aged; Neoplasm Staging; Retrospective Studies; Taxoids; Treatment Outcome

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

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

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