Phase Ib Study of Binimetinib with Paclitaxel in Patients with Platinum-Resistant Ovarian Cancer: Final Results, Potential Biomarkers, and Extreme Responders

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Rachel N GrishamCarol A Aghajanian

Abstract

Purpose: Epithelial ovarian cancer (EOC) is a molecularly diverse disease. MEK inhibition targets tumors harboring MAPK pathway alterations and enhances paclitaxel-induced apoptosis in EOC. This phase Ib study evaluated the MEK inhibitor binimetinib combined with paclitaxel in patients with platinum-resistant EOC.Patients and Methods: Patients received intravenous weekly paclitaxel with oral binimetinib in three different administration schedules. Outcomes were assessed by RECIST and CGIC CA-125 response criteria. Tumor samples were analyzed using next-generation sequencing.Results: Thirty-four patients received ≥1 binimetinib dose. A 30-mg twice-a-day continuous or 45-mg twice-a-day intermittent binimetinib dose was deemed the recommended phase II dose (RP2D) in combination with 80 mg/m2 i.v. weekly paclitaxel. Rate of grade 3/4 adverse events was 65%. The best overall response rate was 18%-one complete (CR) and four partial responses (PR)-among 28 patients with RECIST-measurable disease. Eleven patients achieved stable disease (SD), yielding a clinical benefit rate (CR+PR+SD) of 57%. Response rates, per both RECIST and CA-125 criteria, were highest in the 45-mg twice-a-day continuous cohort and lowest in the 45-mg twice-a-day...Continue Reading

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Jul 30, 2019·Expert Opinion on Investigational Drugs·Erlisa BardhiPierluigi Benedetti Panici
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