KRAS mutation in patients with metastatic colorectal cancer does not preclude benefit from oxaliplatin-or irinotecan-based treatment

Abstract

Fluoropyrimidine-based chemotherapy plus antibody therapy is currently the standard first-line treatment for metastatic colorectal cancer (mCRC). In this study, we investigated the hypothesis that mutations in several of the targeted oncogenes are correlated with treatment outcomes in mCRC patients receiving different first-line regimens. Our study included a total of 194 patients who had undergone various forms of first-line chemotherapy. The KRAS, BRAF, PIK3CA, NRAS and AKT1 mutational status of the tumors was assessed and the association between mutational status and treatment outcome was evaluated. The median progression-free survival (mPFS) of the wild-type and mutated KRAS subgroups that had received oxaliplatin-based treatment was 8.6 and 6.8 months, respectively (P=0.41), whereas the mPFS of the wild-type KRAS, BRAF, PIK3CA, NRAS and AKT1 subgroups and that of their respective mutant subgroups was 9.7 and 7.2 months, respectively (P=0.10). The mPFS of the wild-type and mutated KRAS subgroups that had received irinotecan-based treatments was 7.7 and 9.7 months, respectively (P= 0.43). The mPFS of the wild-type KRAS, BRAF, PIK3CA, NRAS and AKT1 subgroups and that of their respective mutant subgroups was 7.1 and 10.0 months, respectively (P=0.76). Our data indicated that mCRC patients with activation of KRAS, BRAF, PIK3CA, NRAS and AKT1 mutations, even those being treated with oxaliplatin- and irinotecan-based regimens as first-line treatment, may benefit from cytotoxic drug therapy.