Ixabepilone: new perspectives for its use in breast cancer

Despite significant advances in recent years, the drug therapy for breast cancer (BC) is still based on chemotherapy. The introduction of new effective cytostatic agents with a favorable toxicity profile is likely to remain an urgent objective for modern pharmacology in oncology. Ixabepilone, first in a new class of antineoplastic agents, the epothilones, has demonstrated high efficacy in the treatment of breast cancer both in its early stages and in patients, who have received 2 or more lines of chemotherapy. The article discusses the results of major studies, as well as the last meta-analysis of Ixabepilone studies in locally advanced and metastatic breast cancer. It presents the results of two large randomized studies of Ixabepilone in adjuvant regimens in patients with early breast cancer with an unfavourable prognosis.

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A network meta-analysis of fulvestrant vs alternative first-line endocrine therapies for endocrine therapy-naive postmenopausal hormone receptor-positive advanced or metastatic breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e12545 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e12545-e12545 ◽

Cited By ~ 3

Author(s):

Claire Telford ◽

Shweta Takyar ◽

Parth Joshi ◽

Mattias Ekman ◽

Nick Jones

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Hormone Receptor ◽

Proportional Hazards ◽

Meta Analysis ◽

Locally Advanced ◽

Metastatic Breast ◽

First Line ◽

Hormone Receptor Positive ◽

American Society

e12545 Background: Fulvestrant (F) is a selective estrogen degrader for hormone receptor-positive (HR+) locally advanced or metastatic breast cancer (LA/MBC). This network meta-analysis examined the efficacy of F (500 mg) vs alternative endocrine therapies (ETs) for first-line treatment of ET-naïve HR+ LA/MBC. Methods: Randomized controlled trials of first-line F, tamoxifen (Tam), anastrozole (A), exemestane (E), letrozole (L), and toremifene (T) for women (≥18 years) with HR+ LA/MBC and no prior ET were identified in a systematic review of MEDLINE, EMBASE, and Cochrane databases from inception to October 2016. Conference proceedings of the American Society of Clinical Oncology, European Society of Medical Oncology, and San Antonio Breast Cancer Symposium from 2013-2016 were hand searched. Trials of targeted combination therapies were excluded. Studies were checked for heterogeneity. A standard fixed-effect Bayesian network meta-analysis was conducted based on hazard ratios (HRs) and assuming proportional hazards for progression-free and overall survival (PFS/OS). Results: Seven eligible studies (1 Phase [Ph] 2, 5 Ph 3, 1 Ph 2/3) were identified. All had PFS data; five had OS data. Two trials compared F vs A; PFS data were available for both trials; sufficiently mature OS data for F were available from Ph 2 only. The proportional hazards assumption was met for PFS only.F had significantly improved PFS vs Tam (HR 0.57, 95% credibility interval [Crl] 0.44-0.73), A (HR 0.75, 95% Crl 0.62-0.91), E (HR 0.65, 95% Crl 0.47-0.91), and T (HR 0.53, 95% Crl 0.37-0.78). Numerically improved PFS was observed for F vs L (HR 0.81, 95% Crl 0.59-1.11). F had significantly improved OS vs Tam (HR 0.63, 95% Crl 0.40-0.98), A (HR 0.63, 95% Crl 0.42-0.94), and E (HR 0.56, 95% Crl 0.33-0.95). OS was numerically improved with F vs L (HR 0.66, 95% Crl 0.41-1.04). Conclusions: This analysis suggests improved PFS and OS for fulvestrant vs tamoxifen, anastrozole, exemestane, and letrozole, and PFS for fulvestrant vs toremifene. Further analysis should be conducted, using non-proportional hazard methods and more mature OS data, to confirm the OS results.

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Lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in the treatment of HER-2-overexpressing locally advanced or metastatic breast cancer: systematic review and meta-analysis

Core Evidence ◽

10.2147/ce.s50474 ◽

2013 ◽

pp. 69 ◽

Cited By ~ 8

Author(s):

Tobias Botrel ◽

Otávio Clark ◽

Luciano Paladini

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Meta Analysis ◽

Locally Advanced ◽

Metastatic Breast ◽

Her 2

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Efficacy and Safety of the All-Oral Schedule of Metronomic Vinorelbine and Capecitabine in Locally Advanced or Metastatic Breast Cancer Patients: The Phase I-II VICTOR-1 Study

International Journal of Breast Cancer ◽

10.1155/2014/769790 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 26

Author(s):

M. E. Cazzaniga ◽

V. Torri ◽

F. Villa ◽

N. Giuntini ◽

F. Riva ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase I ◽

Cancer Patients ◽

Phase Ii ◽

Locally Advanced ◽

Metastatic Breast ◽

Fixed Dose ◽

Toxicity Profile ◽

Breast Cancer Patients

Background. Vinorelbine (VRB) and capecitabine (CAPE) are demonstrated to be active in pretreated metastatic breast cancer patients. Different studies have demonstrated that the metronomic treatment is active with an acceptable toxicity profile. We designed a Phases I-II study to define the MTD of oral metronomic, VRB, and CAPE.Patients and Methods. Phase I: fixed dose of CAPE was 500 mg thrice a day, continuously. Level I of VRB was 20 mg/tot thrice a week for 3 weeks (1 cycle). Subsequent levels were 30 mg/tot and 40 mg/tot (Level III), respectively, if no Grades 3-4 toxicity were observed in the previous level. Phase II: further 32 patients received the MTD of VRB plus CAPE for a total of 187 cycles to confirm toxicity profile.Results. 12 patients were enrolled in Phase I and 22 in Phase II. Phase I: the MTD of VRB was 40 mg. Phase II: 187 cycles were delivered, observing 5.9% of Grades 3-4 toxicity. 31 patients are evaluable for efficacy, obtaining a clinical benefit rate of 58.1%.Conclusion. MTD of VRB with fixed dose of CAPE was 40 mg thrice a week and was the recommended dose for the ongoing Phase II multicenter study.

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Network meta-analysis of eribulin versus other chemotherapies used as second- or later-line treatment in locally advanced or metastatic breast cancer

BMC Cancer ◽

10.1186/s12885-021-08446-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qi Zhao ◽

Rachel Hughes ◽

Binod Neupane ◽

Kristin Mickle ◽

Yun Su ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Advanced Breast Cancer ◽

Locally Advanced Breast Cancer ◽

Meta Analysis ◽

Locally Advanced ◽

Metastatic Breast ◽

Progression Free Survival ◽

Free Survival

Abstract Background 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. Methods 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). Results 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. Conclusions 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.

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