Association of RAS mutational status with clinical outcomes in metastatic colorectal cancer treated with trifluridine/tipiracil or regorafenib.

Previous studies demonstrated codon-specific mutation as a potential biomarker of resistance in metastatic colorectal cancer (mCRC). Our study aimed to evaluate the association of status on survival in patients with mCRC treated with trifluridine/tipiracil (FTD/TPI) or regorafenib. mCRC Patients treated with FTD/TPI combination (FTD/TPI), FTD/TPI monotherapy (FTD/TPI) or regorafenib were retrospectively enrolled into our study. All patients were classified according to chemotherapy regimen and status. Progression-free survival (PFS) and overall survival (OS) was estimated for comparison. Kaplan–Meier curves were plotted for survival. A total of 263 patients were enrolled into our study, accounting for 79 FTD/TPI, 86 FTD/TPI and 98 regorafenib. The median PFS and OS were 4.9 m, 3.0 m versus 2.5 m and 15.1 m, 11.3 m versus 7.3 m in FTD/TPI, FTD/TPI and regorafenib, respectively. The overall response rate were 23%, 7% versus 5% in FTD/TPI, FTD/TPI and regorafenib, respectively. Patients were stratified according to status, accounting for 129 , 85 and 51 . For patients with , the median OS was 16.2 m, 14.7 m and 6.5 m for FTD/TPI, FTD/TPI and regorafenib, respectively. For patients with , the median OS was 9.5 m, 5.6 m and 8.4 months for FTD/TPI, FTD/TPI and regorafenib group, respectively. For patients with , the median OS was 13.4 m, 9.9 m and 5.0 months for FTD/TPI, FTD/TPI and regorafenib group, respectively. In conclusion, FTD/TPI had superior survival across all mutational status. Notably, regorafenib was associated with longer OS than FTD/TPI monotherapy in the subgroup, whereas FTD/TPI monotherapy yielded longer OS than regorafenib in patients with and status. These results suggest a potential role for status in treatment selection and strongly support the need for prospective, randomized trials to confirm these observations before they can be translated into clinical practice guidelines.