Gene expression profiling in BRAF-mutated melanoma reveals patient subgroups with poor outcomes to vemurafenib that may be overcome by cobimetinib plus vemurafenib

MJ Wongchenko; GA McArthur; B Dreno; J Larkin; PA Ascierto; J Sosman; L Andries; M Kockx; SD Hurst; I Caro; I Rooney; PS Hegde; L Molinero; H Yue; I Chang; L Amler; Y Yan; A Ribas

Journal article

Gene expression profiling in BRAF-mutated melanoma reveals patient subgroups with poor outcomes to vemurafenib that may be overcome by cobimetinib plus vemurafenib

MJ Wongchenko, GA McArthur, B Dreno, J Larkin, PA Ascierto, J Sosman, L Andries, M Kockx, SD Hurst, I Caro, I Rooney, PS Hegde, L Molinero, H Yue, I Chang, L Amler, Y Yan, A Ribas

Clinical Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2017

DOI: 10.1158/1078-0432.CCR-17-0172

Abstract

Purpose: The association of tumor gene expression profiles with progression-free survival (PFS) outcomes in patients with BRAF V600-mutated melanoma treated with vemurafenib or cobimetinib combined with vemurafenib was evaluated. Experimental Design: Gene expression of archival tumor samples from patients in four trials (BRIM-2, BRIM-3, BRIM-7, and coBRIM) was evaluated. Genes significantly associated with PFS (P < 0.05) were identified by univariate Cox proportional hazards modeling, then subjected to unsupervised hierarchical clustering, principal component analysis, and recursive partitioning to develop optimized gene signatures. Results: Forty-six genes were identified as significantly a..

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