Predictive and Prognostic Roles of BRAF Mutation in Stage III Colon Cancer: Results from Intergroup Trial CALGB 89803

摘要: Purpose: Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers colorectal carcinogenesis. In cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined effect of on survival treatment efficacy patients stage III colon cancer. Methods: assessed status c.1799T>A (p.V600E) MSI 506 cancer enrolled a randomized adjuvant chemotherapy trial [5-fluorouracil leucovorin (FU/LV) vs. irinotecan (CPT11), FU LV (IFL); CALGB 89803]. Cox proportional hazards model was used to assess prognostic role mutation, adjusting for clinical features, arm, status. Results: Compared 431 wild-type patients, 75 -mutated experienced significantly worse overall [OS; log-rank P = 0.015; multivariate HR 1.66; 95% CI: 1.05–2.63]. By assessing combined MSI, it seemed that MSS (microsatellite stable) tumor an unfavorable subtype, whereas MSI-high favorable were intermediate subtypes. Among tumors, nonsignificant trend toward improved OS observed IFL versus FU/LV arm (multivariate 0.52; 0.25–1.10). conferred no suggestion benefit beyond alone 1.02; 0.72–1.46). Conclusions: Additional studies necessary whether there any predictive irinotecan-based therapy. Clin Cancer Res; 18(3); 890–900. ©2011 AACR .