On August 2, the U.S. Food and Drug Administration (FDA) approved trifluridine and tipiracil (Lonsurf) with bevacizumab for patients with metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and, if their disease is RAS wild-type, an anti-EGFR therapy. The FDA had previously approved single-agent trifluridine and tipiracil for this indication in September 2015.
Safety and efficacy were evaluated in SUNLIGHT (ClinicalTrials.gov identifier NCT04737187), a randomized, open-label, multicenter, global trial of trifluridine and tipiracil with bevacizumab compared to single-agent trifluridine and tipiracil in 492 patients with metastatic colorectal cancer who received a maximum of two prior chemotherapy regimens and who had progressive disease or displayed intolerance to their last regimen.
The primary efficacy outcome measures were overall survival and progression-free survival. The trial demonstrated a statistically significant overall survival improvement in patients randomly assigned to receive trifluridine and tipiracil plus bevacizumab compared to those receiving only trifluridine and tipiracil (hazard ratio [HR] = 0.61, 95% confidence interval [CI] = 0.49–0.77, one-sided P < .001). Median overall survival was 10.8 months in the trifluridine and tipiracil plus bevacizumab arm (95% CI = 9.4–11.8 months) and 7.5 months in the trifluridine and tipiracil arm (95% CI = 6.3–8.6 months). Median progression-free survival was 5.6 months in the trifluridine and tipiracil plus bevacizumab arm (95% CI = 4.5–5.9 months) and 2.4 months in the trifluridine and tipiracil arm (95% CI = 2.1–3.2 months, HR = 0.44, 95% CI = 0.36, 0.54, one-sided P < .001).
The most common adverse reactions or laboratory abnormalities among patients receiving trifluridine and tipiracil with bevacizumab (≥ 20%) were neutropenia, anemia, thrombocytopenia, fatigue, nausea, increased aspartate aminotransferase, increased alanine transaminase, increased alkaline phosphatase, decreased sodium, diarrhea, 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.
This application was granted Priority Review designation.