On August 2, 2023, the Food and Drug Administration approved trifluridine and tipiracil, for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. FDA had previously approved single-agent trifluridine and tipiracil for this indication in September 2015.

Safety and efficacy were evaluated in SUNLIGHT (NCT04737187), a randomised, open-label, multicenter, global trial of trifluridine and tipiracil, with bevacizumab compared to single-agent trifluridine and tipiracil with bevacizumab in 492 patients with mCRC who received a maximum of two prior chemotherapy regimens and demonstrated progressive disease or intolerance to the last regimen.

The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS). The trial demonstrated a statistically significant OS improvement in patients randomised to the trifluridine and tipiracil, plus bevacizumab arm compared to those randomised to trifluridine and tipiracil (Hazard ratio 0.61; 95% CI: 0.49, 0.77; 1-sided p<0.001). Median OS was 10.8 months in the LONSURF plus bevacizumab arm (95% CI: 9.4, 11.8) and 7.5 months in the trifluridine and tipiracil arm (95% CI: 6.3, 8.6). Median PFS was 5.6 months in the LONSURF plus bevacizumab arm (95% CI: 4.5, 5.9) and 2.4 months in the trifluridine and tipiracil arm (95% CI: 2.1, 3.2) (Hazard ratio 0.44; 95% CI: 0.36, 0.54; 1-sided p<0.001).

The most common adverse reactions or laboratory abnormalities for LONSURF with bevacizumab (≥20%) are neutropenia, anaemia, thrombocytopenia, fatigue, nausea, increased AST, increased ALT, increased alkaline phosphatase, decreased sodium, diarrhoea, abdominal pain, and decreased appetite.

The recommended trifluridine and tipiracil dose is 35 mg/m2 orally twice daily with food on days 1 through 5 and days 8 through 12 of each 28-day cycle. Refer to the Prescribing Information for bevacizumab dosing information.

View complete prescribing information for trifluridine and tipiracil with bevacizumab here. 

Source: FDA