In a subgroup analysis of the phase III TAGS trial (TAS-102 Gastric Study) reported in JAMA Oncology, David H. Ilson, MD, PhD, and colleagues found positive trends in survival benefit with trifluridine/tipiracil treatment vs placebo for patients with pretreated metastatic gastric cancer or gastroesophageal junction cancer who had or had not undergone gastrectomy.
David H. Ilson, MD, PhD
Study Details
The trial included 507 patients from 110 sites in 17 countries in Europe, Asia, and North America who had undergone at least two prior chemotherapy regimens. Patients were randomly assigned 2:1 between February 2016 and January 2018 to receive oral trifluridine/tipiracil at 35 mg/m2 twice daily or placebo twice daily with best supportive care on days 1 through 5 and days 8 through 12 of each 28-day treatment cycle. Overall, 221 patients—including 147 in the trifluridine/tipiracil treatment group and 74 in the placebo group—had undergone gastrectomy, and 286—including 190 in the trifluridine/tipiracil treatment group and 96 in the placebo group—had not undergone gastrectomy.
The primary endpoint was overall survival. A prior report from the trial showed that trifluridine/tipiracil treatment was associated with significantly improved overall and progression-free survival in the overall population. The current preplanned analysis was performed to assess potential trends in the subgroups and was not powered for statistical significance.
Survival Outcomes
In the subgroup of patients who had undergone gastrectomy, median overall survival was 6.0 months in patients treated with trifluridine/tipiracil vs 3.4 months in patients treated with placebo (hazard ratio [HR] = 0.57, 95% confidence interval [CI] = 0.41–0.79), with 6-month rates of 50% vs 24%, respectively, and 12-month rates of 20% vs 9%. Median progression-free survival was 2.2 months vs 1.8 months (HR = 0.48, 95% CI = 0.35–0.65), with 6-month rates of 13% vs 3%.
In the subgroup of patients who had not undergone gastrectomy, median overall survival was 5.6 months vs 3.8 months (HR = 0.80, 95% CI = 0.60–1.06), with rates of 6-month rates of 44% vs 39% and 12-month rates of 22% vs 16%. Median progression-free survival was 1.9 months vs 1.8 months (HR = 0.65, 95% CI =0.49–0.85), with 6-month rates of 16% vs 9%.
KEY POINTS
- Trifluridine/tipiracil appeared to be associated with an overall survival benefit in patients who had undergone gastrectomy and in patients who had not undergone gastrectomy.
- Progression-free survival benefit was also observed in both subgroups.
Adverse Events
Among patients in the trifluridine/tipiracil group, grade ≥ 3 adverse events occurred in 84.1% of patients with prior gastrectomy and 76.3% of patients who had not undergone gastrectomy, including neutropenia in 44.1% vs 26.3%, anemia in 21.4% vs 17.4%, and leukopenia in 14.5% vs 5.3%. Adverse events led to dosing modification in 64.8% vs 53.2% of patients and discontinuation of treatment in 10.3% vs 14.7%.
The investigators concluded, “[Trifluridine/tipiracil] treatment was tolerable and provided efficacy benefits among patients with pretreated metastatic gastric cancer or gastroesophageal junction cancer regardless of previous gastrectomy.”
Dr. Ilson, of the Department of Medicine, Memorial Sloan Kettering Cancer Center, is the corresponding author for the JAMA Oncology article.
Disclosure: This study was funded by Taiho Oncology Inc and Taiho Pharmaceutical Company Limited. For full disclosures of the study authors, visit jamanetwork.com.
