Rachel Grisham

Binimetinib in low-grade serous carcinoma

A phase II study of Selumetinib, an oral small-molecule inhibitor of MEK1/2, has shown promising results in patients with recurrent LGSOC, with a 15% objective response rate. Based on those results, the MILO/ENGOT-ov11 trial was initiated, designed with a primary study objective to compare progression-free survival (PFS) of the MEK-inhibitor Binimetinib vs. physician’s choice of selected chemotherapies (liposomal doxorubicin, weekly paclitaxel or topotecan). A total of 341 women were randomized across 17 countries; 227 patients were treated with Binimetinib, and 106 with physicians’ choice of chemotherapy.The study was closed in 2016 when interim analysis showed that the hazard ratio crossed the predefined futility boundary (observed HR of 1.21).The results of the interim analysis as well as results of an updated analysis with a data cut-off of January 2019 were presented at the International Gynecologic Cancer Society Global Meeting in Rio de Janeiro, Brazil in September, 2019. Binimetinib showed activity in women with low grade serous ovarian cancer across the efficacy endpoints evaluated with a response rate of 24% and a median PFS of 11.2 months (17.7 months in those with KRAS mutation), although this study did not meet its primary endpoint. Chemotherapy responses were higher than predicted based on historical data. The safety results observed in this study are generally consistent with the known safety profile of Binimetinib and with MEK inhibitor class effects. Patients with LGSOC have a median survival of 6-10 years with significant morbidity from their disease, multiple effective therapies are needed. KRAS mutation testing may help to predict which patients with LGSOC are most likely to respond to Binimetinib.

Author: Dr Rachel Grisham, Memorial Sloan Kettering Cancer Center
27 November 2019