Predictive and Prognostic Roles of BRAF Mutation in Stage III Colon Cancer: Results from Intergroup Trial CALGB 89803
Year: 2011
Type: article
Abstract: PURPOSE: Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers in colorectal carcinogenesis. In colorectal cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer. METHODS: We assessed status of BRAF c.1799T>A (p.V600E) mutation and MSI in 506 stage III colon cancer patients enrolled in a randomized adjuvant chemotherapy trial [5-fluorouracil and leucovorin (FU/LV) vs. irinotecan (CPT11), FU and LV (IFL); CALGB 89803]. Cox proportional hazards model was used to assess the prognostic role of BRAF mutation, adjusting for clinical features, adjuvant chemotherapy arm, and MSI status. RESULTS: Compared with 431 BRAF wild-type patients, 75 BRAF-mutated patients experienced significantly worse overall survival [OS; log-rank P = 0.015; multivariate HR = 1.66; 95% CI: 1.05-2.63]. By assessing combined status of BRAF and MSI, it seemed that BRAF-mutated MSS (microsatellite stable) tumor was an unfavorable subtype, whereas BRAF wild-type MSI-high tumor was a favorable subtype, and BRAF-mutated MSI-high tumor and BRAF wild-type MSS tumor were intermediate subtypes. Among patients with BRAF-mutated tumors, a nonsignificant trend toward improved OS was observed for IFL versus FU/LV arm (multivariate HR = 0.52; 95% CI: 0.25-1.10). Among patients with BRAF wild-type cancer, IFL conferred no suggestion of benefit beyond FU/LV alone (multivariate HR = 1.02; 95% CI: 0.72-1.46). CONCLUSIONS: BRAF mutation is associated with inferior survival in stage III colon cancer. Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy.
Source: Clinical Cancer Research
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Pfizer, Massachusetts General Hospital, University of Nebraska Medical Center, Ohio State University, Memorial Sloan-Kettering Cancer Center, Syracuse University, Wake Forest University, University of Missouri, University of Minnesota, Georgetown University, Dartmouth College, University of Illinois at Urbana-Champaign, School of Medicine, Duke University, University of North Carolina at Chapel Hill, Norris Cotton Cancer Center, State University of New York Upstate Medical University, National Cancer Institute, National Center for Research Resources
Awards: G1072356872, G10814802, G1112175344, Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer, G1186831119, G1391839138, G1406545193, G1422427855, G1460768082, G1486637521, G148836555, G149288587, G1551507774, G1570777714, G1689128559, G1790576020, G1814228702, G192656225, G198474791, G199746015, G20154349, G211333722, G2177483498, G220937036, G2261465654, G2281990079, G2288808002, G2296793909, G237383067, G2405064429, G257334932, G260759372, G2647518335, G2652865090, G2709169786, G281275239, G3089953435, G31853261, G3236675860, G3255944410, G3267350032, Southeast Cancer Control Consortium, Inc, G328901006, G3298934708, G3472329976, G3581085865, G3690325657, G3710026009, G3754462075, G3789417232, G3790305154, G3857640367, G4040562365, G4192246825, G4196232189, G4530377164, G4670716055, G4744150602, G4795678184, G532797959, CANCER AND LEUKEMIA GROUP B, G5660033547, G6016746934, G6286696974, G639492384, G6886639697, G7035163513, Hematology-Oncology Associates of Central New York CCOP, G7103307427, G7190461629, G739544170, G763325562, Nevada Cancer Research foundation-Community Clinical Oncology Program, G802218729, G866232813, G8665016104, G877081928, G877907214, G914912716, G926666752, G973482110, G979369470
OpenAlex ID: W2052982012