Chemoimmunotherapy to be explored in metastatic triple-negative breast cancer: eribulin mesylate + pembrolizumab
A study presented at the San Antonio Breast Cancer Symposium (SABCS) in December 2016 is investigating the combination of eribulin mesylate and pembrolizumab in patients with metastatic triple negative breast cancer who have received up to 2 lines of prior chemotherapy. In an interview filmed at SABCS, Sara Tolaney, MD, MPH, Medical Oncologist at Dana-Farber Cancer Institute and Brigham & Women’s Hospital, Boston, USA discussed the design and interim results of this study. Study 218 was a multicentre Phase Ib/II trial. The Phase Ib portion evaluated the safety and tolerability of the combination and established the recommended dose for the Phase II study.1 The primary endpoint of the Phase II study was objective response rate. Interim results of the Phase Ib study show that, among 7 patients who received the full dose of eribulin and pembrolizumab, no dose-limiting toxicities were observed.1 The recommended dosage for the Phase II study was 1.4 mg/m2 eribulin mesilate on days 1 and 8 and pembrolizumab 200 mg on day 1 of a 21-day cycle. In the interim analysis of the Phase II study data (n=32) the objective response rate was 33%.1 The safety profile of the combination was comparable with expected findings with either treatment as monotherapy.1 These include fatigue, peripheral neuropathy, neutropenia and nausea.1
Outcomes for patients with triple negative metastatic breast cancer are much worse than for those other breast cancer subtypes and there is a need for improved therapeutic options for this patient population.1 There has been considerable interest in immunotherapy in triple negative breast cancer and these results offer hope that this treatment regimen may result in better long-term outcomes. There is a need for a follow-up study to determine the durability of the responses. Interestingly, PD-L1 positivity did not seem to predict response to treatment, suggesting that the combination of chemotherapy and immunotherapy has activity regardless of PD-L1 status.1 This finding may broaden the applicability of immunotherapy in triple negative disease.
Eribulin is indicated in the European Union for the treatment of adults with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting unless patients were not suitable for these treatments.
Pembrolizumab is under investigation for the treatment of metastatic triple negative breast cancer.
This article and interview have been initiated and funded by Eisai.