A Real-World Comparison of Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer in the United States

Background: Trifluridine/Tipiracil (TAS-102) and regorafenib are FDA-approved in the United States for treatment of refractory metastatic co-lorectal cancer (mCRC). FDA approvals of these agents were based on modest improvements in overall survival (OS) compared with best sup-portive care + placebo in the RECOURSE and CORRECT trials, respec-tively. This study compared real-world clinical outcomes with the use of these agents. Methods: A nationwide deidentified electronic health re-cord-derived database was reviewed for patients diagnosed with mCRC between 2015 and 2020. Patients who received at least 2 lines of standard systemic therapy followed by treatment with either TAS-102 or regorafenib were included for analysis. Kaplan-Meier and pro-pensity score-weighted proportional hazards models were used to compare survival outcomes between groups. Results: The records of 22,078 patients with mCRC were reviewed. Of these, 1,937 patients received at least 2 lines of standard therapy followed by regorafenib and/or TAS-102. Median OS for the TAS-102 alone or prior regorafe-nib group (n=1,016) was 6.66 months (95% CI, 6.16-7.18 months) compared with 6.30 months (95% CI, 5.80-6.79 months) for regora-fenib alone or prior to TAS-102 (n=921; P=.36). A propensity score- weighted analysis controlling for potential confounders did not demonstrate a significant difference in survival between groups (hazard ratio, 0.99; 95% CI, 0.90-1.09 ; P=.82). A subgroup analysis did not identify any significant differences in outcomes regarding age, performance status, tumor sidedness, microsatellite instability sta-tus, or RAS/RAF status. Conclusions: This analysis of real-world data found that OS was similar for patients with mCRC who were treated with TAS-102 compared with regorafenib. Median OS with both agents in a real-world setting was similar to that shown in the clinical trials that led to their approvals. A prospective trial comparing TAS-102 and re-gorafenib would unlikely change current management of patients with refractory mCRC.