Extended 5-Year Follow-up Results of a Phase Ib Study (BRIM7) of Vemurafenib and Cobimetinib in BRAF-Mutant Melanoma.

Abstract

PURPOSE:

To report the 5-year overall survival (OS) landmark and the long-term safety profile of vemurafenib plus cobimetinib (BRAF plus MEK inhibition, respectively) in the BRIM7 study.

PATIENTS AND METHODS:

This phase Ib, dose-finding, and expansion study evaluated combination treatment with vemurafenib and cobimetinib in two cohorts of patients with advanced BRAF V600-mutated melanoma: patients who were BRAF inhibitor (BRAFi)-naïve (n = 63) or patients who had progressed on prior treatment with BRAFi monotherapy [vemurafenib monotherapy-progressive disease (PD); n = 66]. Patients in the dose-escalation phase received vemurafenib at 720 or 960 mg twice daily in combination with cobimetinib at 60, 80, or 100 mg/d for 14 days on/14 days off, 21 days on/7 days off, or continuously. Two regimens were selected for expansion: vemurafenib (720 and 960 mg twice daily) and cobimetinib (60 mg/d 21/7).

RESULTS:

Median OS was 31.8 months [95% confidence interval (CI), 24.5-not estimable] in the BRAFi-naïve cohort. The landmark OS rate plateaued at 39.2% at years 4 and 5 of follow-up. In the vemurafenib monotherapy-PD cohort, the median OS was 8.5 months (95% CI, 6.7-11.1), and the landmark OS 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.

CONCLUSIONS:

A subset of patients with advanced BRAF V600-mutated melanoma treated with a combination regimen of vemurafenib and cobimetinib achieve favorable long-term outcomes.

• Authors: Antoni Ribas, Adil Daud, Anna C Pavlick, Rene Gonzalez, Karl D Lewis, Omid Hamid, Thomas F Gajewski, Igor Puzanov, Matthew Wongchenko, Isabelle Rooney, Jessie J Hsu, Yibing Yan, Erica Park, Grant A McArthur
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 1 Pg. 46-53 (01 01 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 31732523 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2019 American Association for Cancer Research.

Chemical References

• Azetidines
• Piperidines
• Vemurafenib
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• cobimetinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Azetidines (administration & dosage)
• Cohort Studies
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Male
• Maximum Tolerated Dose
• Melanoma (drug therapy, genetics, pathology)
• Middle Aged
• Mutation
• Patient Safety
• Piperidines (administration & dosage)
• Proto-Oncogene Proteins B-raf (genetics)
• Skin Neoplasms (drug therapy, genetics, pathology)
• Treatment Outcome
• Vemurafenib (administration & dosage)
• Young Adult