VIDEO: MEK/BRAF combo puts brakes on BRAF-mutated advanced melanoma progression

Source: Skin & Allergy News, October 2014

MADRID – Combining the investigational MEK inhibitor cobimetinib with the BRAF inhibitor vemurafenib nearly halved the risk of progression in previously untreated patients with BRAF-mutated advanced melanoma in the ongoing, phase III coBRIM study.

Median progression-free survival by investigator was 6.2 months with vemurafenib (Zelboraf) and 9.9 months with the combination (Hazard ratio 0.51; P less than .0001); by independent review, median progression-free survival was 6.0 months versus 11.3 months, respectively (HR, 0.60; P = .0003), study author Dr. Grant McArthur reported in a late-breaking abstract at the European Society for Medical Oncology Congress.

Combination therapy also resulted in a significantly higher objective response rate (68% vs. 45%; P less than .0001) and more complete responses (10% vs. 4%) among the 495 patients with unresectable, locally advanced or metastatic BRAF V600 mutation–positive disease.

Overall survival data are not yet mature, but the interim analysis showed a promising 35% reduction in the risk of death at 9 months (HR, 0.65), said Dr. McArthur of the Peter MacCallum Cancer Centre, Melbourne, Australia. The corresponding P value of .046 is descriptive, as it did not cross the prespecified stopping boundary for the interim analysis.

Grade 3 toxicity, albeit fairly common, was slightly higher with combination therapy vs. vemurafenib alone (65% vs. 59%). Adverse event–related treatment discontinuations were similar between arms (13% vs. 12%), he said.

The data, which were simultaneously published in the New England Journal of Medicine (2014 Sept. 29 [doi:10.1056/NEJMoa1408868]) are expected to be submitted to the U.S. Food and Drug Administration later this year for potential approval of cobimetinib. Vemurafenib was approved in the United States for late-stage or unresectable melanoma in August 2011.

In our video interview, Dr. McArthur discusses coBRIM and his suggestions for how clinicians may incorporate this novel strategy into practice.

coBRIM was funded by F. Hoffmann-LaRoche/Genentech. Dr. McArthur reported grants from Roche, Novartis, Pfizer, Millennium, and Celegene, and consulting for Provectus.