Phase II study of bevacizumab plus trifluridine/tipiracil and irinotecan as second-line therapy for RAS wild-type metastatic colorectal cancer.

Abstract

e15578 Background: Patients with RAS wild-type (RASwt) metastatic colorectal cancer (mCRC) progressing on first-line fluoropyrimidine-based chemotherapy plus anti-EGFR therapy have limited and often suboptimal second-line treatment options. Trifluridine/tipiracil (TAS-102) is an oral cytotoxic agent that inhibits tumor growth through incorporation into DNA and disruption of DNA function, potentially overcoming fluoropyrimidine resistance. We conducted a phase II study to evaluate the efficacy and safety of bevacizumab combined with TAS-102 and irinotecan in this setting. Methods: In this single-arm phase II trial (ChiCTR2100046678), patients with RASwt mCRC who progressed after first-line anti-EGFR therapy plus chemotherapy received TAS-102 (35 mg/m², days 1–5), bevacizumab (5 mg/kg), and irinotecan (180 mg/m²) every 2 weeks. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From August 2021 to January 2026, 27 patients were enrolled. The median age was 59 years (range, 42-75), male accounted for 81.5%,Most patients (26/27) had an ECOG status of 1. As of data cutoff (January 2026), 24 patients had ≥1 postbaseline tumor assessment; 7 remained on treatment. Best overall responses included partial response in 5 patients (20.8%), stable disease in 18 (75.0%), and progressive disease in 1 (4.2%). The confirmed ORR was 20.8% (95% CI: 3.3–38.4%) and DCR was 95.8% (95% CI: 87.2–100.0%). With a median followup of [X] months, median PFS was 7.7 months (95% CI: 4.99–10.41) and median OS was 20.7 months (95% CI: 8.83–31.31). Grade ≥3 treatmentrelated adverse events (occurring in ≥5% of patients) were neutropenia (40%), leukopenia (24%), anemia (8%), and thrombocytopenia (8%). No treatmentrelated deaths were reported. Conclusions: The combination of bevacizumab, TAS-102, and irinotecan showed promising clinical activity and manageable toxicity as secondline therapy for RASwt mCRC patients who progressed on prior anti-EGFR-based treatment. These results support further evaluation of this regimen in randomized controlled trials. Clinical trial information: ChiCTR2100046678.