Combined BRAF-MEK Inhibitor Therapy in BRAF-Mutant Melanoma
Posted: Friday, June 1, 2018
For patients with advanced BRAF V600–mutant melanoma, the BRAF inhibitor encorafenib plus the MAP2K inhibitor binimetinib treatment showed “favorable efficacy” compared with vemurafenib monotherapy, according to the phase III COLUMBUS trial by Reinhard Dummer, MD, of the University Hospital Zürich Skin Cancer Center, Switzerland; Paolo A. Ascierto, MD, of Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy; and colleagues published in The Lancet Oncology. The combination regimen also demonstrated improved tolerability over encorafenib or vemurafenib alone.
In the trial, 577 patients with locally advanced unresectable or metastatic cutaneous melanoma, or an unknown primary melanoma with a BRAF V600E or V600K mutation, in their tumor tissue were recruited. The combination treatment was given to 192 patients, encorafenib was given to 194 patients, and vemurafenib was given to 191 patients.
At a median follow-up of 16.6 months, the median progression-free survival was 14.9 months with the combination treatment compared with 9.6 months with encorafenib and 7.3 months with vemurafenib. A confirmed overall response was reported in 63% of patients receiving the combination therapy, 51% receiving encorafenib, and 40% receiving vemurafenib.
Fewer grade 3/4 adverse events occurred in the combination therapy group (58%) than in either the encorafenib (66%) or vemurafenib (63%) group. In the group that received encorafenib plus binimetinib, the most common grade 3/4 adverse events were increased g-glutamyltransferase levels (9%), increased creatine phosphokinase levels (7%), and hypertension (6%).
“Overall survival data and long-term safety data will provide additional insights into the efficacy and tolerability of this combination,” concluded the investigators.