On February 22, 2019, the U.S. Food and Drug Administration (FDA) approved a trifluridine and tipiracil tablet (Lonsurf)—a fixed combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor—for adult patients with metastatic gastric or gastroesophageal 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, randomized, 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 randomized 2:1 to receive the trifluridine and tipiracil tablets (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 the trifluridine and tipiracil tablets 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 randomized to the arm taking the trifluridine and tipiracil tablets (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 the trifluridine and tipiracil tablets occurred at a higher rate than in patients receiving placebo and were neutropenia, anemia, nausea, decreased appetite, thrombocytopenia, vomiting, and diarrhea.
The recommended dose and schedule for the trifluridine and tipiracil tablet is 35 mg/m2/dose orally twice daily with food on days one through five and days eight through twelve of each 28-day cycle.
FDA granted this application priority review and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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 or by calling 1-800-FDA-1088.
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