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Clinical Trial
. 2020 Jan 1;26(1):46-53.
doi: 10.1158/1078-0432.CCR-18-4180. Epub 2019 Nov 15.

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

Antoni Ribas  1 , Adil Daud  2 , Anna C Pavlick  3 , Rene Gonzalez  4 , Karl D Lewis  5 , Omid Hamid  6 , Thomas F Gajewski  7 , Igor Puzanov  8 , Matthew Wongchenko  9 , Isabelle Rooney  9 , Jessie J Hsu  9 , Yibing Yan  9 , Erica Park  9 , Grant A McArthur  10
Affiliations
Clinical Trial

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

Antoni Ribas et al. Clin Cancer Res. .

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.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

A.R. reports institutional research grants from Genentech; honoraria for consultancy from Genentech, Roche, Chugai, Novartis, Amgen, Merck, and Bristol-Myers Squibb (BMS); and personal fees for advisory role from Arcus Biosciences, Bioncotech Therapeutics, Compugen, CytomX, Five Prime Therapeutics, FLX Bio, ImaginAb, Kite Pharma, Merus, Rgenix, Tango Therapeutics, and PACT Pharma. A.D. reports personal fees from Merck Sharp & Dohme, Incyte, Genentech/Roche, BMS, Alexion, EMD Serono, and Novartis. A.C.P. reports personal fees from BMS, Seattle Genetics, Genentech/Roche, Merck Sharp & Dohme, Novartis, and Amgen. R.G. reports personal fees from BMS, Incyte, Novartis, and Genentech/Roche. K.D.L. reports personal fees for consultancy from Roche. O.H. reports institutional research support from AstraZeneca, BMS, Celldex Therapeutics, Genentech/Roche, Immunocore, Incyte, Merck, Merck Serono, MedImmune, Novartis, Pfizer, and Rinat Neuroscience, and personal fees for advisory boards and/or speaker bureaus from Genentech/Roche, Amgen, Novartis, BMS, Merck, Array BioPharma, and Sanofi. T.F.G. reports personal fees from Incyte, Alkermes, BMS, Genentech/Roche, Janssen, Merck Sharp & Dohme, Pfizer, and Novartis. I.P. reports personal fees for consultancy from Amgen and Roche. M.W. reports employment with Genentech/Roche and reports stock ownership with Genentech/Roche and ARIAD Pharmaceuticals. I.R. and J.J.H. report employment with Genentech/Roche. Y.Y. and E.P. report employment and stock ownership with Genentech/Roche. G.A.M. reports institutional research grants from Genentech/Roche.

Figures

Figure 1.
Figure 1.
Kaplan–Meier curves for PFS in (A) BRAFi-naive cohort and (B) vemurafenib monotherapy–PD cohort. Abbreviations: BRAFi, BRAF inhibitor; PD, progressive disease; PFS, progression-free survival.
Figure 2.
Figure 2.
Kaplan–Meier curves for OS in (A) BRAFi-naive cohort and (B) vemurafenib monotherapy–PD cohort. BRAFi, BRAF inhibitor; NE, not estimable; OS, overall survival; PD, progressive disease.
See this image and copyright information in PMC

References

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