Safety and efficacy of eribulin in combination with gemcitabine in patients with advanced triple negative breast cancer.

Abstract

e12578 Background: Triple negative breast cancer (TNBC) characterized by aggressive tumor behavior with very poor prognosis following progression after standard chemotherapeutic regimens.The combination of Gemcitabine, a nucleoside analogue, and eribulin a microtubule-targeting agent exhibited synergistic cytotoxic effects in pre-clinicall and clinical setting . Thus, eribulin combined with gemcitabine may synergistically induce tumor cell death, especially in tumors like TNBC. Based on this rationale, we conducted a phase II study evaluating this combination either in first- or in second-line treatment for advanced TNBC.Methods: Females with locally advanced or metastatic TNBC who had received previous chemotherapy , with an ECOG (PS) ≤ 1, and adequate hematological, renal and hepatic function. Patients received eribulin (1mg/m2) plus gemcitabine (1000 mg/m2) on day 1 and 8, q21 until disease progression. CT scans were performed every 12 weeks. The main objective of this trial was to evaluate the overall response rate (ORR) and secondary were Feasibiliy, safety and clinical benefit rate (CBR ). Results: Thirty –two females (median age: 62 years, median ECOG performance status (PS) 1) were enrolled the study. The majority had visceral disease (78.5%). A median of 9 (range:4–18) treatment cycles was administered (69% of patients received ≥ 6 cycles), .All patients were evaluable for response. We did observe 12 partial responses for an overall response rate of 37.5% (95%CI,26.1-57.0). A stable disease was observed in 15 patients (46.8%). Clinical benefit, was observed in 21 patients (65.6%; 95%CI,48.1-76.6). The most common grade 3 or 4 toxicities were haematologic . The main grade 3 or 4 non-hematolgic toxicities were fatigue, diarrhoea, nausea and vomiting. Of the 32 patients in total 7 patients had dose reductions and 14 patients had dose delays. Conclusions: Resistance to current standard therapieslimits the available options for previously treated patients with metastatic TNBC and there is currently no preferred standard chemotherapy. This study demonstrated that the combination of eribulin and gemcitabine was efficacious, feasible and toxicity was generally manageable