KRAS codon 12 and 13 mutations may guide the selection of irinotecan or oxaliplatin in first-line treatment of metastatic colorectal cancer

Background: In this study, we aimed to investigate the frequency, prognostic effect of codon, and amino acid-specific KRAS mutations in patients with metastatic colorectal cancer (mCRC) and their predictive effect on irinotecan and oxaliplatin during first-line treatment. Methods: The data of 304 mCRC patients were retrospectively evaluated between 2010 and 2018. Patients were categorized according to the most prominent codon and amino acid mutation and their prognostic features were analyzed. Results: In total, 274 patients were included in the study and 128 patients (47%) revealed KRAS mutation. Median follow-up time was 19.8 months (range; 1.6-96). The median overall survival rates for patients with codons 12 and 13 mutations were 25.4 and 22.2 months, respectively (p = 0.4). Moreover, the median overall survival for the codon 12 mutant patients who received irinotecan-based chemotherapy in the first-line treatment was 42.7 months, whereas for the codon 13 mutant and KRAS wild-type patients, it was 18.3 and 23.9 months, respectively (codon 12 vs. codon 13; HR: 0.31, p = 0.03, codon 12 vs. wild-type; HR: 0.45, p = 0.03). Conclusion: The significant survival advantage was observed in patients with codon 12 mutations who received irinotecan-based chemotherapy as a first-line treatment.