FDA approves trifluridine and tipiracil with bevacizumab for previously treated metastatic colorectal cancer
Regulatory approval: On Aug 2, 2023, the FDA approved trifluridine/tipiracil (LONSURF) in combination with bevacizumab for previously treated metastatic colorectal cancer. The decision was supported by the randomized SUNLIGHT trial (NCT04737187), in which LONSURF plus bevacizumab improved overall survival versus LONSURF alone (HR 0.61; median 10.8 vs 7.5 months) and progression-free survival (HR 0.44; median 5.6 vs 2.4 months).
FDA approval (Aug 2, 2023): trifluridine/tipiracil + bevacizumab in previously treated mCRC
The US FDA approved trifluridine and tipiracil (LONSURF) with bevacizumab for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biologic therapy, and—if RAS wild-type—an anti-EGFR therapy. FDA previously approved single-agent LONSURF for this indication in September 2015.
Supporting evidence
Safety and efficacy were evaluated in SUNLIGHT (NCT04737187), a randomized, open-label, multicenter global trial comparing LONSURF + bevacizumab vs LONSURF alone in 492 patients with mCRC who had received a maximum of two prior chemotherapy regimens and had progressive disease or intolerance to the last regimen.
Primary endpoints were overall survival (OS) and progression-free survival (PFS):
- OS: HR 0.61 (95% CI 0.49–0.77; 1-sided p<0.001); median 10.8 vs 7.5 months.
- PFS: HR 0.44 (95% CI 0.36–0.54; 1-sided p<0.001); median 5.6 vs 2.4 months.
Safety and dosing
Common adverse reactions/lab abnormalities (≥20%) with the combination included neutropenia, anemia, thrombocytopenia, fatigue, nausea, transaminase elevations, alkaline phosphatase increase, hyponatremia, diarrhea, abdominal pain, and decreased appetite.
Recommended LONSURF dose: 35 mg/m² orally twice daily with food on days 1–5 and 8–12 of each 28-day cycle; refer to bevacizumab prescribing information for dosing. The application received priority review.