The evidence supporting this protocol is provided by a phase III multicentre international open-label randomised trial (EMBRACE) involving 762 patients comparing Eribulin monotherapy with treatment of physician's choice (TPC) in patients with metastatic breast cancer.r
Between Nov 2006 and Nov 2008, 508 patients were randomised to receive eribulin mesilate 1.4 mg/m2 days 1 and 8 every 21 days and 254 patients were randomised to receive TPC (defined as any single-agent chemotherapy, hormonal, biological treatment, radiotherapy or symptomatic treatment alone). The TPC arm consisted of 97% chemotherapy (26% vinorelbine, 18% gemcitabine, 18% capecitabine, 16% taxane, 9% anthracycline, 10% other chemotherapy), and 3% hormonal therapy. Treatment in both arms continued until disease progression, unacceptable toxicity, patient or physician request to discontinue or serious protocol non-compliance.r
The primary end point was overall survival and secondary end points were progression-free survival, objective response rates, and duration of response.r
A second phase III randomised trial (NCT00337103 – Study 301) involving over 1100 patients comparing eribulin with capecitabine in patients with advanced or metastatic breast cancer. Women with metastatic breast cancer who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Co-primary endpoints were overall survival (OS) and progression free survival (PFS). This trial did not demonstrate superiority of eribulin versus capecitabine for either OS or PFS.r
Eribulin improved overall survival to 13.1 vs 10.6 months in the TPC arm (HR = 0.81, 95% CI 0.66-0.99, p=0.041). Median PFS times for eribulin and TPC were 3.7 months and 2.2 months respectively (HR=0.87, 95% CI, 0.71-1.05, p = 0.137). The objective response rates were 12% for eribulin and 5% for TPC (p = 0.002).r
Kaplan-Meier analysis of overall survival (intention-to-treat population) for EMBRACE trial r
© Lancet Oncology 2011
Median OS times for eribulin and capecitabine were 15.9 and 14.5 months respectively (HR=0.88; 95% CI, 0.77 to 1.00; P = 0.056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = 0.30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms.r
Kaplan-Meier analysis of overall survival (intention-to-treat population) for STUDY 301 r
© Journal of Clinical Oncology 2015
The predominant toxicities grade 3 or 4 adverse events that occurred more often with eribulin than with TPC were neutropenia, leucopenia, and peripheral neuropathy.
Febrile neutropenia occurred in approximately 5% (23 of 503 patients) of patients treated with eribulin. Approximately 18% of patients in the eribulin arm received G-CSF.
Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin in 5% of patients. In patients with grade 3 or 4 peripheral neuropathy who continued treatment, neuropathy improved to grade 2 or lower in later cycles after delays and dose reductions. Alopecia was reported in 45% of patients receiving eribulin.
Fatal treatment-related adverse events occurred in five (1%) patients receiving eribulin (febrile neutropenia, lung infection, and bronchopneumonia in one patient each, dyspnoea in two patients) and two (1%) patients receiving TPC (febrile neutropenia, aspergillosis in one patient each).
© Lancet Oncology 2011