Impact of KRAS codon-specific mutations on survival in metastatic colorectal cancer on TAS-102 with or without bevacizumab

Codon-specific KRAS mutations have been implicated as predictive biomarkers for efficacy of trifluridine/tipiracil (TAS-102) in metastatic colorectal cancer (mCRC). However, their predictive impact for TAS-102 plus bevacizumab (Tas-Bev), the new standard in mCRC, is unknown. A real-world retrospective study at MD Anderson Cancer Center (Houston, TX) and Tempus AI (Chicago,IL) investigated this impact in patients receiving TAS-102 or TAS-Bev. A total of 946 mCRC patients were evaluated; KRAS was mutated in 57.8% of patients; 39.4% involving the G12 codon and 9.8% G13. There was no association of KRAS-G12 mutations with overall survival (p=0.441) on TAS-102 contradicting the reported predictive impact of these biomarkers. Moreover, the overall survival was inferior for KRAS-G13 mutant patients (p=0.045). On TAS-Bev, no association was found between KRAS-G12 (p=0.188) or KRAS-G13 (p=0.072) mutations and overall survival. The authors conclude that further research is needed to assess the impact of these mutation on combined TAS-Bev therapy prior to any clinical application.