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Impact of the Specific Mutation in KRAS Codon 12 Mutated Tumors on Treatment Efficacy in Patients with Metastatic Colorectal Cancer Receiving Cetuximab-Based First-Line Therapy: A Pooled Analysis of Three Trials

Modest D.P.a · Brodowicz T.d, e · Stintzing S.a · Jung A.b · Neumann J.b · Laubender R.P.c · Ocvirk J.d, f · Kurteva G.d, g · Papai Z.d, h · Knittelfelder R.d · Kirchner T.b · Heinemann V.a · Zielinski C.C.d, e
aDepartment of Medicine III, University Hospital Grosshadern, and Institutes of bPathology and cMedical Informatics, Biometry, and Epidemiology, University of Munich, Munich, Germany; dCentral European Cooperative Oncology Group, and eClinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; fInstitute of Oncology, Ljubljana, Slovenia; gSBALO National Oncology Center, Sofia, Bulgaria; hAEK Onkologiai Osztaly, Budapest, Hungary Oncology 2012;83:241–247 (DOI:10.1159/000339534)

Abstract

Purpose: This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC). Patients: Overall, 119 patients bearing a KRAS mutation in codon 12 were evaluated. All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group (CECOG), AIO KRK-0104 or AIO KRK-0306 trials. Results: Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens. Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations (overall survival 23.3 vs. 14–18 months; hazard ratio 0.66, range 0.43–1.03). An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab. Conclusion: The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy.

 

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