KRAS Mutation in Stage III Colon Cancer and Clinical Outcome Following Intergroup Trial CALGB 89803
Year: 2009
Type: article
Abstract: PURPOSE: Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy (cetuximab or panitumumab). It remains uncertain, however, whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy. METHODS: We conducted a study of 508 cases identified among 1,264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) in 1999-2001 (CALGB 89803). KRAS mutations were detected in 178 tumors (35%) by pyrosequencing. Kaplan-Meier and Cox proportional hazard models assessed the prognostic significance of KRAS mutation and adjusted for potential confounders including age, sex, tumor location, tumor/node stage, performance status, adjuvant chemotherapy arm, and microsatellite instability status. RESULTS: Compared with patients with KRAS-wild-type tumors, patients with KRAS-mutated tumors did not experience any difference in disease-free, recurrence-free, or overall survival. The 5-year disease-free, recurrence-free, and overall survival rates (KRAS-mutated versus KRAS-wild-type patients) were 62% versus 63% (log-rank P = 0.89), 64% versus 66% (P = 0.84), and 75% versus 73% (P = 0.56), respectively. The effect of KRAS mutation on patient survival did not significantly differ according to clinical features, chemotherapy arm, or microsatellite instability status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. CONCLUSIONS: In this large trial of chemotherapy in stage III colon cancer patients, KRAS mutational status was not associated with any significant influence on disease-free or overall survival.
Source: Clinical Cancer Research
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer, WUMC Cancer and Leukemia Group B, BAPTIST CANCER INSTITUTE COMMUNITY CLINICAL ONCOLOGY PRO, Cancer and Leukemia Group B, Dietary And Lifestyle Determinants Of Colon Cancer Recurrence and Survival, North Shore CCOP, Cancer and Leukemia Group B, G2647518335, Minority Based Community Clinical Oncology Program, Cancer and Leukemia Group B Statistical Center, SOUTHWEST ONCOLOGY GROUP STATISTICAL CENTER, University of Iowa CALGB Institutional Grant, Southeast Cancer Control Consortium, Inc, Cancer and Leukemia Group B, Cancer and Leukemia Group B, G379387698, CANCER AND LEUKEMIA GROUP B, TOLEDO COMMUNITY CLINICAL ONCOLOGY PROGRAM, Molecular Epidemiology of Colorectal Cancer, Cancer and Leukemia Group B, CANCER AND LEUKEMIA GROUP B, Cancer and Leukemia Group B, Southwest Oncology Group, Delaware/Christiana Care Community Clinical Oncology Program, Cancer and Leukemia Group B, OSU as Network Lead Academic Participating Site for the NCI NCTN, Heartland Cancer Research CCOP, Hematology-Oncology Associates of Central New York CCOP, MOUNT SINAI COMMUNITY CLINICAL ONCOLOGY PROGRAM, Cancer and Leukemia Group B, Multidisciplinary Clinical and Translational Science (MCTS) Program (UL1), Cancer and Leukemia Group B - The Ohio State University, Nevada Cancer Research foundation-Community Clinical Oncology Program, ECOG Statistical Office, G973482110
OpenAlex ID: W2104573387