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

No Thumbnail Available

Date

2012

Journal Title

Journal ISSN

Volume Title

Publisher

American Association for Cancer Research
The Harvard community has made this article openly available. Please share how this access benefits you.

Research Projects

Organizational Units

Journal Issue

Citation

Ogino, S., K. Shima, J. A. Meyerhardt, N. J. McCleary, K. Ng, D. Hollis, L. B. Saltz, et al. 2011. “Predictive and Prognostic Roles of BRAF Mutation in Stage III Colon Cancer: Results from Intergroup Trial CALGB 89803.” Clinical Cancer Research 18 (3): 890–900. https://doi.org/10.1158/1078-0432.ccr-11-2246.

Research Data

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% Cl: 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% Cl: 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% Cl: 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. Clin Cancer Res; 18(3); 890-900.

Description

Other Available Sources

Keywords

Terms of Use

This article is made available under the terms and conditions applicable to Other Posted Material (LAA), as set forth at Terms of Service

Endorsement

Review

Supplemented By

Referenced By

Related Stories