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

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 (KRAS G12 ) mutation and no KRAS G12 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 KRAS G12 mutation, 50% had RAS/RAF WT , 9% had KRAS G13 mutation, 8% had KRAS other mutation, 3% had NRAS mutation and 2% had BRAF mutation. For patients treated with TAS-102 group, 20% patients had KRAS G12 mutation, while for regorafenib group, 38% patients had KRAS G12 mutation. The median OS of TAS-102 was 4.5 versus 11.3 months for KRAS G12 mutation and no KRAS G12 mutation, respectively (p= 0.013). The median OS of regorafenib was 10.5 versus 6.3 months for KRAS G12 mutation and no KRAS G12 mutation, respectively (p= 0.183). Furthermore, 34% patients with KRAS G12 mutation received TAS-102, while 56% patients without KRAS G12 mutation received TAS-102. For patients with KRAS G12 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 KRAS G12 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 KRAS G12 was divergent between mCRC patients treated with TAS-102 and regorafenib. Codon-specific KRAS mutational status should be taken into consideration before treatment.