Tislelizumab combined with bevacizumab and trifluridine/tipiracil as third-line or later therapy for metastatic colorectal cancer (mCRC) : A real-world study.

Abstract

e15554 Background: Microsatellite stable (MSS) patients (pts) account for 95% of metastatic colorectal cancer (mCRC) cases and respond poorly to immunotherapy (IO). IOs + anti-angiogenic agents have shown promising preclinical antitumor activity. This real-world study evaluated the efficacy and safety of bevacizumab plus trifluridine/tipiracil and tislelizumab in late-line MSS metastatic colorectal cancer (mCRC), and assess benefit in patients with liver metastases. Methods: This single-center, prospective real-world study enrolled mCRC patients (ECOG PS 0/1) progressing after ≥2 prior therapies. They received trifluridine/tipiracil (35 mg/m² BID, days 1-5 & 8-12/28-day cycle), bevacizumab (5 mg/kg, days 1 & 15), and tislelizumab (200 mg, day 1/21-day cycle). The primary endpoint was progression-free survival (PFS). The secondary outcomes included overall survival (OS) and the objective response rate (ORR) per RECIST 1.1. Results: As of Jan.23, 2026, 35 evaluable patients were included. The median PFS was 7.95 months (95% CI: 5.26–12.02), with 1-year and 2-year PFS rates of 35.4%, and 16.1%, respectively. The ORR was 17.1% (6/35; 3 with liver metastases) and the DCR was 77.1%. Median OS was 16.56 months (95% CI: 10.94–24.71), with survival rates of 62.9% at 1 year, and 36.4% at 2 years. Outcomes differed by metastasis status: in patients with liver metastases (n = 21), median PFS was 5.88 months (95% CI: 4.83–10.32) and median OS of 13.27 months (95% CI: 8.21–22.60). In those without liver metastases (n = 14), median PFS(13.14 months ,95% CI: 2.43–18.17) and OS (22.95 months, 95% CI:6.34–NR) were significantly longer. Grade ≥3 treatment-related adverse events occurred in 57.1% of patients, primarily neutropenia (40.0%). Immune-related adverse events (all grade 1-2) were observed in 34.3% of patients, without increased hepatotoxicity in the liver metastasis subgroup. Early grade 3 neutropenia and decreased neutrophil-to-lymphocyte ratio (NLR) were noted in 8/10 patients with OS > 2 years. Conclusions: This combination shows promising activity and manageable safety in late-line MSS mCRC. Patients without liver metastases had significantly longer PFS and OS. Early NLR reduction may predict better outcomes. Clinical trial information: NCT05314101 .