Trifluridine/Tipiracil in Heavily Pretreated Metastatic Gastric Cancer
In the phase III TAGS trial reported in The Lancet Oncology, Shitara et al found that trifluridine/tipiracil (Lonsurf) significantly improved overall survival vs placebo in patients with heavily pretreated metastatic gastric cancer.
In the double-blind trial, 507 patients with nonresectable metastatic gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) from 110 sites in 17 countries were randomly assigned 2:1 between February 2016 and January 2018 to receive oral trifluridine/tipiracil at 35 mg/m² twice daily on days 1 to 5 and days 8 to 12 every 28 days plus best supportive care (n = 337) or placebo plus best supportive care (n = 170). Patients had to have received ≥ 2 prior chemotherapy regimens and to have radiologic disease progression. Overall, 66% to 72% of patients were white and 15% to 17% were Asian. Approximately 63% of patients had received at least 3 prior chemotherapy regimens.
The primary endpoint was overall survival in the intent-to-treat population.
Overall Survival
Median overall survival was 5.7 months (95% confidence interval [CI] = 4.8–6.2 months) in the trifluridine/tipiracil group vs 3.6 months (95% CI = 3.1–4.1 months) in the placebo group (hazard ratio [HR] = 0.69, P = .00058). At 1 year, 21% vs 13% of patients remained alive.
Hazard ratios were similar for white patients (0.77, 95% CI = 0.60–0.99) and Asian patients (0.77, 95% CI = 0.46–1.28). Median progression-free survival was 2.0 months vs 1.8 months (HR = 0.57, P < .0001).
Adverse Events
Grade ≥ 3 adverse events occurred in 80% of the trifluridine/tipiracil group and 58% of the placebo group, with the most common being neutropenia (34%) and anemia (19%) in the trifluridine/tipiracil group and abdominal pain (9%) and general deterioration of physical health (9%) in the placebo group. Serious adverse events occurred in 43% vs 42% of patients. One treatment-related death occurred in each group, due to cardiopulmonary arrest in a patient treated with trifluridine/tipiracil and toxic hepatitis in a patient treated with placebo.
The investigators concluded, “Trifluridine/tipiracil significantly improved overall survival compared with placebo and was well tolerated in this heavily pretreated population of patients with advanced gastric cancer. Trifluridine/tipiracil could be a new treatment option in this population who represent a high unmet medical need.”
The study was funded by Taiho Oncology and Taiho Pharmaceutical.
Kohei Shitara, MD, of the National Cancer Center Hospital East, Kashiwa, Japan, is the corresponding author for The Lancet Oncology article.
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