On February 22, 2019, the FDA approved a new indication for trifluridine plus tipiracil (Lonsurf; Taiho Pharmaceuticals), an oral combination of a nucleoside metabolic inhibitor and a thymidine phosphorylase inhibitor for the treatment of patients with metastatic gastric or gastroesophageal junction adenocarcinoma who received ≥2 lines of chemotherapy regimens with a fluoropyrimidine, a platinum, a taxane or irinotecan, and, if appropriate, HER2/neu-targeted therapy. The FDA used its priority review process for this new indication and granted it an orphan drug designation. Trifluridine plus tipiracil was previously approved for metastatic colorectal cancer.
The FDA approved this new indication for the fixed combination of trifluridine and tipiracil based on the results of the international, randomized, placebo-controlled TAGS clinical trial that included 507 patients with metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were randomized to trifluridine plus tipiracil and best supportive care or to placebo and best supportive care. The median overall survival was 5.7 months with trifluridine plus tipiracil versus 3.6 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.56-0.58; P = .0006). The progression-free survival was also significantly longer with the combination than with placebo (P <.00001).
The most common (≥10%) adverse events associated with trifluridine plus tipiracil in this study included neutropenia, anemia, diarrhea, decreased appetite, nausea, thrombocytopenia, and vomiting.
