Association of BRAF V600E/K Mutation Status and Prior BRAF/MEK Inhibition With Pembrolizumab Outcomes in Advanced Melanoma: Pooled Analysis of 3 Clinical Trials.

JAMA Oncology
Igor PuzanovOmid Hamid

Abstract

The optimal sequencing of immune checkpoint inhibitors and targeted therapy for BRAF V600E/K-mutant melanoma is not well established. To assess the association of BRAF wild-type (WT) or BRAF V600E/K-mutant status and BRAF inhibitor (BRAFi) with or without MEK inhibitor (MEKi) therapy with response to pembrolizumab. This study is a post hoc subgroup analysis of pooled data from 3 multinational, multisite studies: KEYNOTE-001 (data cutoff September 1, 2017), KEYNOTE-002 (data cutoff May 30, 2018), and KEYNOTE-006 (data cutoff December 4, 2017). Patients included in this analysis were adults with advanced melanoma and known BRAF V600E/K tumor status who had received pembrolizumab. Patients received pembrolizumab in dosages of 2 mg/kg every 3 weeks, 10 mg/kg every 2 weeks, or 10 mg/kg every 3 weeks. End points were objective response rate (ORR) and progression-free survival (PFS) assessed by Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival (OS). Objective response rates, 4-year PFS, and OS rates were compared in the following patient subgroups: BRAF WT vs BRAF V600E/K-mutant melanoma and BRAF V600E/K-mutant melanoma with vs without previous treatment with BRAFi with or without MEKi therapy. The overal...Continue Reading

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Citations

Mar 28, 2021·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K RzeniewiczS Turajlic
Apr 3, 2021·The Journal of Investigative Dermatology·Franziska Noelle HarbersFang Zhao
Apr 6, 2021·Seminars in Cancer Biology·Benjamin ShumSamra Turajlic
Mar 25, 2021·Hematology/oncology Clinics of North America·Lilit Karapetyan, John M Kirkwood
Apr 20, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Marcel WieswegMartin Schuler
Jul 31, 2021·World Journal of Diabetes·Carly YimTerra Arnason
Jul 12, 2021·Neoplasia : an International Journal for Oncology Research·Haris BabačićMaria Pernemalm
Aug 16, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Anne ZarembaLisa Zimmer
Aug 21, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Samantha J SeitterStephanie L Goff

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