Lonsurf Receives FDA Approval for Recurrent, Metastatic Gastric and Gastroesophageal Junction Cancer

For recurrent or metastatic disease previously treated with at least 2 lines of chemotherapy, involving gastric and gastroesophageal junction cancer, treatment with trifluridine / tipiracil tablets (Lonsurf) received, on 22 February 2019, FDA approval.

Mechanism of action: Lonsurf combines 2 molecules, trifluridine and tipiracil. Trifluridine is a nucleoside analog, while tiripasil is a thymidine phosphorylase inhibitor. Trifluridine enters DNA during DNA synthesis , inhibiting tumor-cell growth. Tipiracil prevents rapid trifluridine metabolism and increased interactions after entry into the body.

The approval is based on TAGS, an international, randomized, double-blind, placebo-controlled clinical trial in patients with metastatic gastric or gastroesophageal (stomach-esophagus) junction adenocarcinoma previously treated with at least two chemotherapy lines, involving 507 patients.

Patients were assigned in a 2-to-1 ratio to two arms. In 337 patients, Lonsurf was given twice daily at 35 mg/m2 with best supportive care (BSC), while 170 patients received placebo plus BSC. Drug treatments were administered in each 28-day cycle on days 1-5. and 8-12.

Study Results

• Median survival was 5.7 months with Lonsurf and 3.6 months with placebo. For patients at this stage, Lonsurf reduced the risk of death by % 31 compared with placebo.
• Lonsurf reduced the risk of cancer progression by %44 compared with placebo. In TAGS, Lonsurf adverse effects occurring more frequently than with placebo were neutropenia, anemia, nausea, decreased appetite, thrombocytopenia, vomiting, and diarrhea (at a frequency of ≥ %10).

The recommended Lonsurf dose is, in each 28-day cycle on days 1 to 5 and 8 to 12, oral tablets twice daily with food at 35 mg/m2.