taxane and Brain-Neoplasms

Cases of human epidermal growth factor receptor 2 (HER2)-positive breast cancer represent approximately 15% to 20% of all breast cancers. Historically, this subtype of breast cancer was associated with an increased risk for the development of systemic and brain metastases and poor overall survival. The introduction of trastuzumab dramatically changed the outcomes of patients with HER2-positive disease, with many demonstrating outcomes similar to those of patients with luminal tumors. Currently, the first-line standard of care for patients with HER2-positive metastatic breast cancer is dual HER2 antibody therapy with pertuzumab/trastuzumab plus a taxane. After progression, the standard of care is trastuzumab emtansine (T-DM1). Although the treatment choices for patients whose disease has progressed on these agents are more limited, promising new drugs have emerged as effective options, including tucatinib and trastuzumab deruxtecan, which were recently approved by the US Food and Drug Administration. Finding the best treatment sequencing for each patient, developing reliable predictive biomarkers, and understanding the mechanisms of resistance to these drugs are necessary to maximize patient outcomes and quality of life. In this review, we analyze the management strategies for metastatic HER2-positive breast cancer, address specific situations, such as the treatment of patients with brain metastases, and discuss future directions in the treatment of this subtype.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Camptothecin; Female; Humans; Immunoconjugates; Neoplasm Metastasis; Oxazoles; Pyridines; Quinazolines; Receptor, ErbB-2; Taxoids; Trastuzumab

Breast cancer consists of a heterogeneous group of diseases, with a number of tumor-specific and patient-specific factors, which influence response to therapy and survival. Ixabepilone is a member of a novel class of antineoplastic agents, the epothilones, that has demonstrated activity in a number of human solid tumor types and is the first agent in this class to be approved by the Food and Drug Administration (FDA) for the treatment of metastatic or locally advanced breast cancer, that is resistant/refractory to anthracyclines, taxanes, and/or capecitabine. Both retrospective and prospective studies have been conducted to evaluate the efficacy of ixabepilone in various populations. The role of ixabepilone in poor prognosis subgroups of the metastatic breast cancer population is reviewed in this article.

Topics: Adult; Aged; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Clinical Trials, Phase III as Topic; Drug Approval; Drug Delivery Systems; Drug Resistance, Neoplasm; Epothilones; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Patient Selection; Prognosis; Randomized Controlled Trials as Topic; Survival Analysis; Taxoids; Treatment Outcome; United States; United States Food and Drug Administration

First-line bevacizumab combined with chemotherapy significantly improves efficacy versus chemotherapy alone in human epidermal growth factor receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer (LR/mBC). This large, open-label study further assesses first-line bevacizumab with taxane-based chemotherapy in routine oncology practice.. Patients with HER2-negative LR/mBC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of zero to two and no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks plus taxane-based chemotherapy (or other non-anthracycline chemotherapy) until disease progression, unacceptable toxicity or patient withdrawal. The primary end point was safety; time to progression (TtP) was a secondary end point.. Median follow-up in 2251 treated patients was 12.7 months. Median age was 53 years and 94% of patients had ECOG PS of zero or one. Bevacizumab was most commonly administered with single-agent paclitaxel (35%), single-agent docetaxel (33%) or taxane-based combination therapy (10%). The most frequent grade ≥3 adverse event (AE) was neutropenia (5.4%). Grade ≥3 AEs previously associated with bevacizumab included hypertension (4.4%), arterial/venous thromboembolism (3.2%), proteinuria (1.7%) and bleeding (1.4%). No new bevacizumab safety signals were observed. Median TtP was 9.5 months (95% confidence interval 9.1-9.9).. The study population in ATHENA was more representative of general oncology practice than populations enrolled into randomised trials, although there may have been some bias towards younger, fitter patients. The safety and efficacy of bevacizumab-taxane therapy in this large study were consistent with results from randomised first-line trials.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Taxoids; Treatment Outcome; Young Adult

A multicenter, open-label, phase 2 study evaluated the efficacy and safety of intravenous vinflunine as third-line treatment in patients with progressing metastatic breast cancer (MBC) after failure of anthracycline- and taxane-based chemotherapy.. Fifty-six patients with MBC, relapsing after receiving 2 previous treatments for advanced disease, including both anthracyclines and taxanes, received 320 mg/m(2) of vinflunine once every 3 weeks (median number of 2.5 cycles, range: 1-13).. According to an independent radiologist, the response rate was 12.5% (95% CI: 5.2-24.1) and 14% (95% CI: 5.3-27.9) (6 partial responses) in the treated and evaluable populations, respectively. Disease control was achieved in 42.9% and 51.2% of the patients, respectively. Median progression-free survival was 2.6 months (95% CI: 1.6-4.0 months) with a median overall survival of 11.4 months (95% CI: 7.4-14.2 months). Duration of response was 6.8 months (95% CI: 5.6 months, upper limit not reached). Leukopenia was the most frequent hematologic toxicity, with grade 3/4 severity in 49.1% of the patients. Grade 3 neutropenia in 30.9%, grade 4 in 40.0% of patients, febrile neutropenia (5.4%), and 1 case of neutropenia infection (1.8%) were reported. Other grade 3 toxicities included anemia (5.5%), fatigue (14.3%), and constipation (7.1%), which were noncumulative. The adverse events associated with vinflunine were predictable and manageable.. Vinflunine is an active and well-tolerated agent as third-line treatment of patients with MBC after failure of anthracycline- and taxane-based therapy. These results warrant further investigation of vinflunine monotherapy or in combination for the treatment of MBC.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Female; Humans; Middle Aged; Neoplasm Staging; Taxoids; Treatment Failure; Vinblastine

To quantify the prevalence of neurological complications among breast cancer patients at one and three years after diagnosis, and to identify factors associated with neuropathic pain (NP) and chemotherapy-induced peripheral neuropathy (CIPN).. Prospective cohort study including 475 patients with newly diagnosed breast cancer, recruited among those proposed for surgical treatment (Portuguese Institute of Oncology, Porto). Patients underwent a neurological evaluation and had their cognitive function assesses with the Montreal Cognitive Assessment, before treatment and at one and three years after enrollment. We estimated the prevalence of each neurological complication, and odds ratios (OR), adjusted for socio-demographic and clinical characteristics, to identify factors associated with NP and CIPN.. More than half of the patients [54.7%, 95% confidence interval (95%CI): 50.2-59.2] presented at least one neurological complication, at one or at three years after cancer diagnosis. Between the first and the third year of follow-up, there was an increase in the prevalence of NP (from 21.1% to 23.6%), cognitive impairment (from 7.2% to 8.2%), cerebrovascular disease (from 0.6% to 1.5%) and brain metastasis (from 0.0% to 0.6%). The prevalence of CIPN decreased from 14.1% to 12.6%. Axillary lymph node dissection was associated with NP at one year (OR = 2.75, 95%CI: 1.34-5.63) and chemotherapy with NP at three years (OR = 2.10, 95%CI: 1.20-3.67). Taxane-based chemotherapy was strongly associated with prevalence of CIPN at one and three years.. Neurological complications are frequent even three years after cancer diagnosis and NP remained the major contributor to the burden of these conditions among survivors.

Topics: Adult; Antineoplastic Agents; Axilla; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Intraductal, Noninfiltrating; Cerebrovascular Disorders; Cognitive Dysfunction; Female; Follow-Up Studies; Humans; Lymph Node Excision; Middle Aged; Neuralgia; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Prevalence; Prospective Studies; Risk Factors; Survivors; Taxoids

Symptomatic brain metastases (BM) occur frequently after chemoradiotherapy (CRT) for stage III NSCLC. Aim of the current study was to determine whether the specific chemotherapy used in a CRT regimen influences BM development.. Retrospective multicenter study including all consecutive stage III NSCLC who completed CRT. Primary endpoints: symptomatic BM development, whether this was the only site of first relapse. Differences between regimens were assessed with a logistic regression model including known BM risk factors and the specific chemotherapy: concurrent versus sequential (cCRT/sCRT), within cCRT: daily low dose cisplatin (LDC)-cyclic dose polychemotherapy; LDC-(non-)taxane cyclic dose; LDC-polychemotherapy subgroups of ≥50 patients.. Between January 2006 and June 2014, 838 patients were eligible (737 cCRT, 101 sCRT). 18.2% developed symptomatic BM, 8.0% had BM as only site of first relapse. BM patients were significantly younger, female, had more advanced N-stage and had adenocarcinoma histology. In both cCRT and sCRT BM were found in 18% (p=0.904). In cyclic dose cCRT (N=346) and LDC (N=391) BM were found in 18.8% and 17.9%, respectively (p=0.757). In 7.2% and 8.7%, respectively, BM were the only site of first relapse (p=0.463). The chemotherapy used (cCRT versus sCRT) had no influence on BM development, not for all brain relapses nor as only site of first relapse (OR 0.88 (p=0.669), OR 0.93 (p=0.855), respectively). LDC versus cyclic dose cCRT was not significantly different: neither for all brain relapses nor as only site of first relapse (OR 0.96 (p=0.819), OR 1.21 (p=0.498), respectively). Comparable results were found for LDC versus cyclic dose non-taxane (N=277) and cyclic dose taxane regimens (N=69) and for cCRT regimens with ≥50 patients (LDC versus cisplatin/etoposide (N=188), cisplatin/vinorelbin (N=65), weekly cisplatin/docetaxel (N=60)).. approximately 18% developed symptomatic BM after stage III diagnosis, not dependent on type of chemotherapy regimen used within a CRT treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain; Brain Neoplasms; Bridged-Ring Compounds; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Combined Modality Therapy; Docetaxel; Etoposide; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Retrospective Studies; Risk Factors; Survival Analysis; Taxoids; Treatment Outcome; Vinblastine; Vinorelbine

It is unclear whether patients undergoing trimodality therapy (TMT) should be screened or surveyed for brain metastases.. We retrospectively analyzed esophageal cancer (EC) patients who underwent TMT between the years 2000 and 2010. All were systematically staged and surveyed but none had screening or surveillance brain imaging.. The median follow-up time for 518 patients was 29.3 months (range 1-149.2); all patients had adenocarcinoma of the esophagus. Of 188 (36.3%) patients who developed distant metastases, 20 (10.6% of 188 patients or 3.9% of 518 patients) had brain metastases. A higher baseline clinical stage (stage III or IVa) was associated with brain metastases. Most (90%) patients with brain metastases were diagnosed within 24 months of surgery. Sixteen patients had central nervous system symptoms at diagnosis. Twelve (60%) patients had solitary metastasis and 8 (40%) patients had multiple metastases. Although 17 patients received therapy for brain metastases, the median overall survival time of 20 patients was only 10.5 months (95% CI 6.6-14.0).. After TMT, 3.9% of EC patients developed brain metastases and their prognosis was poor. Our data suggest that screening and/or surveillance for brain metastases in the EC population undergoing TMT is not warranted.

Topics: Adenocarcinoma; Adult; Aged; Brain Neoplasms; Bridged-Ring Compounds; Chemoradiotherapy; Combined Modality Therapy; Dose Fractionation, Radiation; Early Detection of Cancer; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Platinum Compounds; Retrospective Studies; Survival Rate; Taxoids; Young Adult