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Association of BRAF V600E/K Mutation Status and Prior BRAF/MEK Inhibition With Pembrolizumab Outcomes in Advanced Melanoma

Association of BRAF V600E/K Mutation Status and Prior BRAF/MEK Inhibition With Pembrolizumab... Key PointsQuestionDoes BRAF V600E/K mutation status or previous BRAF inhibitor (BRAFi) with or without MEK inhibitor (MEKi) therapy affect response to pembrolizumab in patients with advanced melanoma? FindingsThis post hoc analysis of 3 randomized clinical trials (KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006) involved 1558 patients with advanced melanoma and known BRAF tumor status (BRAF wild-type or BRAF V600E/K-mutant melanoma) who had all been treated with pembrolizumab and some of whom had undergone prior treatment with BRAF inhibitors with or without MEK inhibitors. Patients with BRAF wild-type and BRAF V600E/K–mutant melanoma had objective response rates (ORRs) of 39.8% and 34.3%, respectively, and similar respective rates of 4-year progression-free survival (PFS; 22.9% and 19.8%) and overall survival (OS; 37.5% and 35.1%); patients with BRAF V600E/K–mutant melanoma who had vs had not received previous BRAFi with or without MEKi had baseline characteristics with worse prognosis: lower ORR (28.4% vs 44.2%), 4-year PFS (15.2% vs 27.8%), and OS (26.9% vs 49.3%). MeaningThe results of this study support the use of pembrolizumab for the treatment of advanced melanoma regardless of BRAF V600E/K mutation status or prior BRAF inhibitor with or without MEK inhibitor therapy. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Oncology American Medical Association

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References (33)

Publisher
American Medical Association
Copyright
Copyright 2020 American Medical Association. All Rights Reserved.
ISSN
2374-2437
eISSN
2374-2445
DOI
10.1001/jamaoncol.2020.2288
Publisher site
See Article on Publisher Site

Abstract

Key PointsQuestionDoes BRAF V600E/K mutation status or previous BRAF inhibitor (BRAFi) with or without MEK inhibitor (MEKi) therapy affect response to pembrolizumab in patients with advanced melanoma? FindingsThis post hoc analysis of 3 randomized clinical trials (KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006) involved 1558 patients with advanced melanoma and known BRAF tumor status (BRAF wild-type or BRAF V600E/K-mutant melanoma) who had all been treated with pembrolizumab and some of whom had undergone prior treatment with BRAF inhibitors with or without MEK inhibitors. Patients with BRAF wild-type and BRAF V600E/K–mutant melanoma had objective response rates (ORRs) of 39.8% and 34.3%, respectively, and similar respective rates of 4-year progression-free survival (PFS; 22.9% and 19.8%) and overall survival (OS; 37.5% and 35.1%); patients with BRAF V600E/K–mutant melanoma who had vs had not received previous BRAFi with or without MEKi had baseline characteristics with worse prognosis: lower ORR (28.4% vs 44.2%), 4-year PFS (15.2% vs 27.8%), and OS (26.9% vs 49.3%). MeaningThe results of this study support the use of pembrolizumab for the treatment of advanced melanoma regardless of BRAF V600E/K mutation status or prior BRAF inhibitor with or without MEK inhibitor therapy.

Journal

JAMA OncologyAmerican Medical Association

Published: Aug 16, 2020

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