On 22 February 2019, the US Food and Drug Administration (FDA) approved trifluridine/tipiracil tablets (LONSURF, Taiho Pharmaceutical Co., Ltd.)—a fixed combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor—for adult patients with metastatic gastric or gastro-oesophageal junction (GEJ) adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.
Approval was based on TAGS (NCT02500043), an international, randomised, double-blind, placebo-controlled trial in 507 patients with metastatic gastric or GEJ adenocarcinoma previously treated with at least two prior lines of chemotherapy. Patients were randomised 2:1 to receive Lonsurf (n=337) 35 mg/m2 orally twice daily on days 1-5 and 8-12 of each 28-day cycle with best supportive care (BSC) or matching placebo (n=170) with BSC until disease progression or unacceptable toxicity.
Median overall survival was 5.7 months (4.8, 6.2) for patients receiving Lonsurf and 3.6 months (3.1, 4.1) for those receiving placebo (hazard ratio: 0.69; 95% CI: 0.56, 0.85; p = 0.0006). Progression-free survival was also longer in patients randomised to the Lonsurf arm (hazard ratio 0.56; 95% CI: 0.46, 0.68; p < 0.0001).
In the TAGS trial, the most common adverse reactions or laboratory abnormalities (≥10% incidence) in patients treated with Lonsurf occurring at a higher rate than in patients receiving placebo were neutropenia, anaemia, nausea, decreased appetite, thrombocytopenia, vomiting, and diarrhoea.
The recommended Lonsurf dose and schedule is 35 mg/m2/dose orally twice daily with food on days 1 through 5 and days 8 through 12 of each 28-day cycle.
Full prescribing information for LONSURF is available here.
FDA granted this application priority review and orphan drug designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.