Impact of KRAS codon-specific mutations on survival in metastatic CRC on trifluridine-tipiracil with/without bevacizumab
Menée dans un contexte de vie réelle à partir de données portant sur 946 patients atteints d'un cancer colorectal métastatique traité par trifluridine/tipiracil avec ou sans bévacizumab, cette étude de cohorte rétrospective évalue l'effet, sur la survie, de mutations KRAS au niveau des codons 12 et 13
Background: Clinical benefit from later lines of therapy in metastatic colorectal cancer (mCRC) is limited. Patient selection for treatment is crucial for optimal risk-benefit evaluation. Codon-specific KRAS mutations have been implicated as predictive biomarkers for efficacy of trifluridine/tipiracil (TAS-102). However, their predictive impact for TAS-102 plus Bevacizumab (TAS-Bev), the new standard of care in mCRC, is unknown.
Methods: This large patient-based, real-world, retrospective cohort study of mCRC patients who received TAS-102 alone or in combination with bevacizumab between January 1, 2020 and March 1, 2023. A sensitivity analysis was performed in two independent cohorts from MD Anderson Cancer Center, Houston, TX and Tempus, AI, Inc., Chicago, IL, prior to polling the data together.
Results: A total of 946 mCRC patients were evaluated; KRAS was mutated in 57.8% cases, 39.4% involving G12 codon and 9.8% G13. We found no association of KRAS-G12 mutations with overall survival (HR = 1.1; 95%CI : 0.90–1.25; p = .441) on TAS-102 contradicting the reported predictive impact of these biomarkers. Moreover, we reported inferior OS for KRAS-G13 mutant patients (HR = 1.3; 95%CI : 1.02–1.69; p = .045). On TAS-Bev, no association was found between KRAS-G12 (HR = 0.8; 95%CI : 0.59-1.11; p = .188) or KRAS-G13 (HR = 1.66; 95%CI : 0.99–2.79, p = .072) mutations and overall survival.
Conclusions: In conclusion, no significant associations between KRAS-G12 and overall survival were found for TAS-102 or TAS-Bev. Further research is needed to assess the impact of these mutations on combined TAS-Bev therapy prior to any clinical application.
Journal of the National Cancer Institute , résumé, 2026