FDA Approves Treatment for Gastric Cancers

The U.S. Food and Drug Administration approved the oral agent trifluridine/tipiracil to treat adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma who previously received at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, human epidermal growth factor receptor 2/neu-targeted therapy.

Study findings: Trifluridine/tipiracil versus placebo

The approval was based on data from the global, randomized, phase III TAGS trial that randomized patients 2:1 to receive trifluridine/tipiracil 35 mg/m2 twice daily on days 1 to 5 and 8 to 12 of each 28-day cycle plus best supportive care or placebo plus best supportive care. Between February 24, 2016, and January 5, 2018, 507 patients were enrolled from 110 academic hospitals in 17 countries: 337 received trifluridine/tipiracil group and 170 received placebo.

The trial met its primary and secondary endpoints, demonstrating prolonged overall survival (OS) with trifluridine/tipiracil. Median overall survival was 5.7 months (95% CI, 4.8-6.2) in the trifluridine/tipiracil group and 3.6 months (95% CI, 3.1-4.1) in the placebo group (hazard ratio = 0.69; 95% CI, 0.56-0.85; one-sided P=0.00029, two-sided P=0.00058). The 12-month OS rate was 21% for those receiving trifluridine/tipiracil versus 13% for the placebo group.

The safety profile of trifluridine/tipiracil was consistent with prior experience with this drug. Grade ≥3 adverse events (AEs) occurred in 267 patients (80%) in the trifluridine/tipiracil group and 97 (58%) in the placebo group. The most frequent grade ≥3 AEs were neutropenia (n=114; 34%) and anemia (n=64; 19%) in the trifluridine/tipiracil group and abdominal pain (n=15; 9%) and general deterioration of physical health (n=15; 9%) in the placebo group. Serious AEs occurred in 143 patients (43%) in the trifluridine/tipiracil group and 70 (42%) in the placebo group. One treatment-related death was reported in each group due to cardiopulmonary arrest in the trifluridine/tipiracil group and toxic hepatitis in the placebo group.

Full results of the study were published in The Lancet Oncology.

Trifluridine/tipiracil is also approved for the treatment of colorectal cancer.