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Type: Journal article
Title: Impact of KRAS and BRAF gene mutation status on outcomes from the phase III AGITG MAX Trial of capecitabine alone or in combination with Bevacizumab and Mitomycin in advanced colorectal cancer
Author: Price, T.
Hardingham, J.
Lee, C.
Weickhardt, A.
Townsend, A.
Wrin, J.
Chua, A.
Shivasami, A.
Cummins, M.
Murone, C.
Tebbutt, N.
Citation: Journal of Clinical Oncology, 2011; 29(19):2675-2682
Publisher: Amer Soc Clinical Oncology
Issue Date: 2011
ISSN: 0732-183X
Statement of
Timothy J. Price, Jennifer E. Hardingham, Chee K. Lee, Andrew Weickhardt, Amanda R. Townsend, Joseph W. Wrin, Ann Chua, Aravind Shivasami, Michelle M. Cummins, Carmel Murone and Niall C. Tebbutt
Abstract: Purpose: Mutations affecting the KRAS gene are established predictive markers of outcome with anti–epithelial growth factor receptor (EGFR) antibodies in advanced colorectal cancer (CRC). The relevance of these markers for anti–vascular endothelial growth factor (VEGF) therapy is controversial. This analysis was performed to assess the predictive and prognostic impact of KRAS and BRAF gene mutation status in patients receiving capecitabine with bevacizumab (CG) or capecitabine without bevacizumab in the phase III AGITG MAX (Australasian Gastrointestinal Trials Group MAX) study. Patients and Methods: Mutation status was determined for 315 (66.9%) of the original 471 patients. Mutation status was correlated with efficacy outcomes (response rate, progression-free survival [PFS], and overall survival [OS]), and a predictive analyses was undertaken. Results: Mutations in KRAS and BRAF genes were observed in 28.8% and 10.6% of patients, respectively. KRAS gene mutation status (wild type [WT] v mutated [MT]) had no prognostic impact for PFS (hazard ratio [HR], 0.89; CI, 0.69 to 1.14) or OS (HR, 0.97; CI, 0.73 to 1.28). BRAF mutation status (WT v MT) was not prognostic for PFS (HR, 0.80; CI, 0.54 to 1.18) but was prognostic for OS (HR, 0.49; CI, 0.33 to 0.73; P = .001). By using the comparison of capecitabine versus capecitabine and bevacizumab (CB) and CB plus mitomycin (CBM), KRAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS (test for interaction P = .95 and 0.43, respectively). Similarly, BRAF gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS (test for interaction P = .46 and 0.32, respectively). Conclusion: KRAS gene mutation status was neither prognostic for OS nor predictive of bevacizumab outcome in patients with advanced CRC. BRAF gene mutation status was prognostic for OS but was not predictive of outcome with bevacizumab.
Keywords: Humans
Colorectal Neoplasms
ras Proteins
Proto-Oncogene Proteins B-raf
Antineoplastic Combined Chemotherapy Protocols
Antibodies, Monoclonal
Treatment Outcome
DNA Mutational Analysis
Genes, ras
Aged, 80 and over
Middle Aged
Antibodies, Monoclonal, Humanized
Rights: © 2011 by American Society of Clinical Oncology
DOI: 10.1200/JCO.2010.34.5520
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