Abstract
BACKGROUND: Both regorafenib and trifluridine/tipiracil (TAS-102) monotherapies have shown significant but limited survival benefits in metastatic colorectal cancer (mCRC) cases who progress after standard treatments. This study aimed to evaluate the efficacy and safety of regorafenib plus biweekly TAS-102 in refractory mCRC. METHODS: In this single-arm multicenter phase II trial (ChiCTR2300071752), eligible patients received regorafenib at 120 mg/day for 21 days in a 4-week cycle or were treated with a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day). TAS-102 was administered biweekly (30 mg/m2 bid on days 1-5). The primary endpoint was progression-free survival (PFS). The secondary endpoints included safety, response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: Between March 1, 2022 and December 1, 2023, 28 patients were enrolled. Totally 24 patients had at least one response evaluation. Median PFS and OS were 4.9 months (95% CI, 4.2-5.6) and 15.4 months (95% CI, 11.1-19.7). The ORR was 8.3% and the DCR was 83.3%. Grade 3 or 4 treatment-related adverse events occurred in 21.4% of patients, including hypertension (7.1%), neutropenia (7.1%), thrombocytopenia (3.6%), and hoarseness (3.6%). CONCLUSIONS: Regorafenib plus biweekly TAS-102 showed promising benefits in refractory mCRC cases, and adverse events were generally tolerable and manageable. DISCUSSION: (ClinicalTrials.gov Identifier: ChiCTR2300071752. IRB Approved: KYLL-202203-026-1.).