A phase Ib study evaluating the safety and long-term benefit of combination treatment with the BRAF inhibitor vemurafenib plus the MEK1 inhibitor cobimetinib in patients with advanced BRAF V600E–mutated melanoma has found that nearly 40% of the patients experienced extended survival of 4 to 5 years after study entry. In addition, long-term treatment with the combination therapy achieved late conversions from partial to complete responses and did not result in unexpected long-term toxicities, according to findings published by Antoni Ribas, MD, and colleagues in Clinical Cancer Research.
Antoni Ribas, MD
The 5-year survival rate for metastatic melanoma among patients diagnosed between 2009 and 2015 was 24.8%, according to statistics from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program.
Study Background and Methodology
The results from this phase Ib study provide extended follow-up results from earlier findings of the phase I BRIM7 trial, which evaluated vemurafenib in combination with cobimetinib in patients with advanced BRAF V600E–mutated melanoma. The earlier results showed that 87% of patients who received the combination and had not been previously treated with a BRAF-targeted therapy had a partial or complete response. This expansion study includes follow-up results from the trial, including overall survival data.
For this study, the researchers enrolled two cohorts of patients with advanced BRAF V600-mutant melanoma. The first cohort included 63 patients who were BRAF inhibitor–naive. The second cohort included 66 patients who had progressed on prior treatment with vemurafenib monotherapy. The data cutoff for this follow-up study was May 25, 2018.
The median overall survival was 31.8 months (95% confidence interval [CI] = 24.5–not estimable] in the BRAF inhibitor–naive cohort, and the landmark overall survival rate plateaued at 39.2% at years 4 and 5 of follow-up. In the vemurafenib monotherapy/progressive disease cohort, the median overall survival was 8.5 months (95% CI = 6.7–11.1), and the landmark overall survival rate plateaued at 14.0% from 3 years of follow-up. No increase was observed in the frequency and severity of adverse events with long-term follow-up. No new toxicities were detected, and there was no increase in the frequency of symptomatic MEK inhibitor class-effect adverse events.
“Combination therapy with vemurafenib and cobimetinib can result in a significant rate of long-term responses and a plateau in the survival curve of patients with BRAF V600–mutated metastatic melanoma. Long-term treatment achieved late conversions from partial to complete responses, and it did not result in unexpected long-term toxicities,” concluded the study authors.
“When this study was initiated, the treatments available yielded long-term benefit at 4 or 5 years for only about 10% of patients diagnosed with metastatic melanoma,” said first study author Dr. Ribas, Professor in the Department of Medicine at the University of California, Los Angeles and the Jonsson Comprehensive Cancer Center, in a statement. “The fact that a subgroup of patients were alive and well at the 5-year follow-up mark after this combination is remarkable.…With the goal of increasing the number of patients with long-term benefit, clinical trials investigating dual BRAF and MEK inhibition with PD-1– or PD-L1–blocking antibodies are currently underway.”
Dr. Ribas is the corresponding author of this study.
Disclosures: Funding for this study was provided by F. Hoffmann-La Roche Ltd. For full disclosures of the study authors, visit clincancerres.aacrjournals.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.