97PPhase II trial of eribulin and S-1 combination therapy for advanced or recurrent breast cancer

Background: Eribulin is a non-taxane microtubule dynamics inhibitor that has been proven to prolong overall survival in patients with breast cancer. S-1, an oral anticancer drug, has demonstrated non-inferiority in overall survival (OS) to taxane as first-line chemotherapy for metastatic breast cancer (MBC). We previouly reported phase I trial results for the combination of these drugs with an overall response rate of 41.7% and median progression free survival (PFS) of 7.6 months. George W et.al (J Clin Oncol 2003) suggested that estrogen receptor negativity, the presence of three or more sites of disease, a short disease-free interval (1 to 24 months), and prior systemic therapy all predicted for impaired overall survival in their multivariate analysis. Considering these factors, we conducted a multicenter phase II study of this combination to further evaluate its safety and efficacy. Methods: Recurrent or advanced breast cancer patients previously treated with anthracycline or taxanes were enrolled from September 2014 to May 2016. Patients received Eribulin 1.4 mg/m2 day1 and day8 intravenously and S-1 50 mg/m2 from day1 to day14 orally. Primary objective was to investigate safety and efficacy. Secondary objectives were to evaluate PFS, OS and clinical benefit rate (CBR) using Response Criteria in Solid Tumors (RECIST). Results: Thirty-two patients were enrolled this trial and 30 patients were evaluable. Objective response rate was 36.7%. There were 3 [10%] complete responses, 8 [26.7%] partial responses and 11 [36.7%] stable diseases. This combination therapy had a manageable safety profiles consistent with the known adverse effects of both drugs. The most common grade3-4 adverse events were neutropenia (22 [73.3%] of 32 patients), leukopenia (13 [43.3%] of 32 patients), febrile neutropenia (3 [9.4%] of 32 patients) and peripheral neuropathy (4 [12.5%] of 32 patients). CBR was 46.7%. The median overall survival and the median PFS was not reached. Conclusions: We showed tolerability and clinical activity in this combination therapy in a subset of patients with poor prognosis. Eribulin in combination with S-1 may represent a promising treatment option for advanced or recurrent breast cancer patients. Legal entity responsible for the study: Eisai Funding: Eisai Disclosure: All authors have declared no conflicts of interest.