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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

Qi Zhao, Rachel Hughes, Binod Neupane, Kristin Mickle, Yun Su, Isabelle Chabot, Marissa Betts, Ananth Kadambi

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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.