Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAF^V600E-Mutant Colorectal Cancer.

ABSTRACT: Although BRAF inhibitor monotherapy yields response rates >50% in BRAF^V600-mutant melanoma, only approximately 5% of patients with BRAF^V600E colorectal cancer respond. Preclinical studies suggest that the lack of efficacy in BRAF^V600E colorectal cancer is due to adaptive feedback reactivation of MAPK signaling, often mediated by EGFR. This clinical trial evaluated BRAF and EGFR inhibition with dabrafenib (D) + panitumumab (P) ± MEK inhibition with trametinib (T) to achieve greater MAPK suppression and improved efficacy in 142 patients with BRAF^V600E colorectal cancer. Confirmed response rates for D+P, D+T+P, and T+P were 10%, 21%, and 0%, respectively. Pharmacodynamic analysis of paired pretreatment and on-treatment bi

SUBMITTER: Corcoran RB 

PROVIDER: S-EPMC5882509 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature