Abstract
Patients diagnosed with metastatic colorectal cancer (mCRC) face a constrained therapeutic landscape following the failure of initial treatment. This multicenter, single-arm, phase II trial (NCT06202001) aimed to assess the efficacy and safety of a novel second-line regimen comprising trifluridine/tipiracil (TAS-102), irinotecan, and bevacizumab. Patients with mCRC resistant to prior fluoropyrimidine and oxaliplatin-based chemotherapy were enrolled. Based on a preceding phase I trial, patients received biweekly cycles of oral TAS-102 (30 mg/m² twice daily, days 1-5), intravenous irinotecan (150 mg/m²), and intravenous bevacizumab (5 mg/kg). The primary outcome measure was the objective response rate (ORR). From October 2023 to August 2024, 60 patients were enrolled. As of December 2024, the ORR was 18.3% (2 complete and 9 partial responses), and the disease control rate (DCR) was 83.3%. The median progression-free survival (PFS) was 6.6 months (95% CI, 4.39-8.81), and the median overall survival (OS) was 17.3 months (95% CI, 13.55-21.05). Subgroup analyses indicated that prior resection of the primary tumor was associated with significantly longer median OS (21.9 vs. 16.2 months; p = 0.048) and PFS (8.9 vs. 5.2 months; p = 0.004). The most frequently reported treatment-related adverse events (TRAEs) were nausea (100%), neutropenia (86.7%), and anemia (83.3%). The predominant grade 3/4 TRAEs included neutropenia (48.3%), febrile neutropenia (8.3%), and diarrhea (6.7%). In conclusion, the combination of irinotecan, TAS-102, and bevacizumab shows encouraging efficacy and a manageable safety profile as a second-line therapy for mCRC, meriting further investigation.