Trifluridine/Tipiracil Plus Bevacizumab for Third-Line Treatment of Refractory Metastatic Colorectal Cancer: The Phase 3 Randomized SUNLIGHT Study

Background

• Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (Bev) demonstrated promising efficacy in a randomized phase 2 trial of heavily pretreated patients (pts) with metastatic colorectal cancer (mCRC). SUNLIGHT was conducted to confirm these findings.

Methods

• The global phase 3 SUNLIGHT study enrolled pts aged ≥18 years with histologically confirmed mCRC, ECOG PS 0/1, and treated with 1-2 prior chemotherapy regimens in an advanced setting, including fluoropyrimidines, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody (if medically considered) and/or anti-EGFR monoclonal antibody for RAS wild-type tumors.
• Pts were randomised (1:1) to receive FTD/TPI (35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle) alone or combined with Bev (5 mg/kg on days 1 and 15). Primary endpoint was overall survival (OS).

Results

• Between Nov 2020 and Feb 2022, 492 patients were randomized to receive FTD/TPI + Bev (n = 246) or FTD/TPI (n = 246).
• Baseline characteristics were balanced between arms.
• FTD/TPI + Bev significantly extended OS over FTD/TPI, median OS was 10.8 months vs 7.5 months, respectively (HR, 0.61; 95% CI, 0.49, 0.77; P< 0.001).
• OS rates at 12 months were 43% in the FTD/TPI + Bev arm and 30% in the FTD/TPI arm.
• Median progression-free survival was 5.6 months in the FTD/TPI + Bev arm and 2.4 months in the FTD/TPI arm (HR, 0.44; 95% CI, 0.36,0.54; P< 0.001).
• Grade ≥3 adverse events (AEs) were not significantly increased in the FTD/TPI + Bev arm vs the FDT/TPI arm (72.4% vs 69.5%).
• No new safety signals were noted.

Conclusions

• FTD/TPI + Bev provided a statistically significant and a clinically meaningful 3.3-month improvement in OS, extending mOS up to 10.8 months, with a 39% reduction in the HR of death in pts with refractory mCRC and with a predictable and acceptable safety profile.

Tabernero J, Prager GW, Fakih M et al. Trifluridine/tipiracil plus bevacizumab for third-line treatment of refractory metastatic colorectal cancer: The phase 3 randomized SUNLIGHT study. Abstract presented at: 2023 ASCO Gastrointestinal Cancers Symposium, January 19-21, 2023.

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