Effectiveness and Safety of Regorafenib vs. Trifluridine/Tipiracil in Unresectable Colorectal Cancer: A Retrospective Cohort Study

A nationwide database was used to compare regorafenib and trifluridine/tipiracil (TFTD) treatment results. This study is the first in which TFTD resulted in significantly longer survival than did regorafenib when used singly. Side effects occurred more commonly with regorafenib than with TFTD. Compared with single-agent use, the use of both regorafenib and TFTD resulted in prolonged survival, regardless of order. Introduction: Compared with the best supportive care, a survival benefit of using regorafenib and trifluridine/tipiracil (TFTD) in patients with colorectal cancer has been shown in previous randomized controlled trials (RCTs). However, there is no RCT or large-scale observational study directly comparing regorafenib and TFTD. Patients and Methods: We used a nationwide claims database in Japan and compared the effectiveness of regorafenib and TFTD for metastatic colorectal cancer during 2013 to 2018. The patients were divided into 4 groups (regorafenib monotherapy, regorafenib/TFTD: regorafenib followed by TFTD, TFTD monotherapy, and TFTD/regorafenib: TFTD followed by regorafenib). Overall survival (OS) and adverse events were compared between the groups. In a subgroup analysis, we also compared treatment effectiveness between the group in which regorafenib was administered first and the group in which TFTD was administered first. Results: We identified 7279 patients (regorafenib: 1501, regorafenib/TFTD: 973, TFTD: 3777, and TFTD/regorafenib: 1028). The corresponding median OS was 6.4, 16.4, 10.2, and 16.9 months, respectively. A log-rank test showed significant intergroup differences (P<.001). In the subgroup analysis, the group in which TFTD was administered first showed significantly longer OS. The incidences of most adverse events were the lowest in the TFTD group. The TFTD group showed longer OS than the regorafenib group, and sequential drug use resulted in the most prolonged OS. Conclusion: Our findings indicate that it might be better to prescribe TFTD first. Furthermore, owing to the longer OS than monotherapy, sequential administration of regorafenib and TFTD ought to be considered. (C) 2020 Elsevier Inc. All rights reserved.