Prognostic impact of codon-specific KRAS mutational status on survival in patients with metastatic colorectal cancer treated with TAS-102 or regorafenib.

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75 Background: Previous study demonstrated KRAS (Kirsten rat sarcoma virus) codon G12 mutation as a potential biomarker of resistance in metastatic colorectal cancer (mCRC). Our study aimed to evaluate the prognostic impact of codon-specific KRAS mutational status on survival in patients with mCRC treated with TAS-102 or regorafenib. Methods: mCRC Patients treated with TAS-102 or regorafenib were retrospectively enrolled into our study. Patients were classified into KRAS G12 (KRASG12) mutation and no KRASG12 mutation according to extended RAS testing. Survival was estimated for comparison, stratified by KRAS mutational status and treatment. Kaplan-Meier curves were estimated for overall survival (OS). Results: A total of 183 patients were enrolled into our study, with 91 patients treated with TAS-102 and 92 patients treated with regorafenib. The median age was 63 years old in our cohort. Most patients were male (54%) with left side colon (85%). After extended RAS/RAF mutational testing, 28% patients had KRASG12 mutation, 50% had RAS/RAFWT, 9% had KRASG13 mutation, 8% had KRASother mutation, 3% had NRAS mutation and 2% had BRAF mutation. For patients treated with TAS-102 group, 20% patients had KRASG12 mutation, while for regorafenib group, 38% patients had KRASG12 mutation. The median OS of TAS-102 was 4.5 versus 11.3 months for KRASG12 mutation and no KRASG12 mutation, respectively (p= 0.013). The median OS of regorafenib was 10.5 versus 6.3 months for KRASG12 mutation and no KRASG12 mutation, respectively (p= 0.183). Furthermore, 34% patients with KRASG12 mutation received TAS-102, while 56% patients without KRASG12 mutation received TAS-102. For patients with KRASG12 mutation, the median OS was 4.5 m versus 10.5 months for TAS-102 and regorafenib group, respectively (p= 0.113). For patients without KRASG12 mutation, the median OS was 11.3m versus 6.3 months for TAS-102 and regorafenib group, respectively (p= 0.047). Conclusions: The prognostic impact of KRASG12 was divergent between mCRC patients treated with TAS-102 and regorafenib. Codon-specific KRAS mutational status should be taken into consideration before treatment.

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