Phase lb safety study of farletuzumab, carboplatin and pegylated liposomal doxorubicin in patients with platinum-sensitive epithelial ovarian cancer

Objective. Farletuzumab is a humanized monoclonal antibody that binds to folate receptor alpha, over expressed in epithelial ovarian cancer (EOC) but largely absent in normal tissue. Previously, carboplatin plus pegylated liposomal doxorubicin showed superior progression-free survival and an improved therapeutic index compared with carboplatin/paclitaxel in relapsed platinum-sensitive EOC. This study assessed safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive recurrent EOC. Methods. This multicenter, single-arm study enrolled patients with platinum-sensitive EOC in first or second relapse for treatment with weekly farletuzumab 2.5 mg/kg plus carboplatin AUC(5-6) and pegylated liposomal doxorubicin 30 mg/m(2) every 4 weeks for 6 cycles. Subsequently, maintenance with single-agent farletuzumab 2.5 mg/kg once weekly or farletuzumab 7.5 mg/kg once every three weeks continued until progression. The primary objective was to assess the safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin. Results. Fifteen patients received a median of 12.0 cycles (range, 3-26) of farletuzumab as combination therapy or maintenance, for a median of 45.0 weeks (range 9-95). Farletuzumab/carboplatin/pegylated liposomal doxorubicin was generally well tolerated, with no farletuzumab-related grades 3-4 adverse events. The most commonly reported adverse events were associated with combination chemotherapy: fatigue (733%), nausea (46.7%), and neutropenia (40%). Ten patients had grade adverse events, most frequently neutropenia and fatigue. No cardiac toxicity was seen. Best overall responses (RECIST) were a complete response for one patient, partial responses for 10 patients, and stable disease for four patients. Conclusions. Farletuzumab plus carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive EOC demonstrated a safety profile consistent with that of carboplatin plus pegylated liposomal doxorubicin. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license