Trifluridine Plus Tipiracil Improves Survival for Patients With Metastatic Gastric, GEJ Cancers Regardless of Age

According to a subgroup analysis from the phase 3 TAGS study, the combination of trifluridine and tipiracil is a safe and effective treatment option in heavily pretreated patients with metastatic gastric/gastroesophageal junction (GEJ) cancers aged ≥65 years.

The trial enrolled 507 patients with metastatic gastric/GEJ cancers from 110 sites in 17 countries who were given ≥2 prior therapies from February 24, 2016, to January 5, 2018. Participants were randomized in a 2:1 ratio to receive trifluridine and tipiracil (n = 337) or placebo (n = 170), plus best supportive care.

The primary endpoint of the study was overall survival (OS), and secondary endpoints included progression-free survival (PFS), safety, and tolerability. Treatment was continued until disease progression, unacceptable toxicity, or patient withdrawal occurred.

The investigators behind this subgroup analysis evaluated the efficacy, safety, and time until treatment discontinuation from any cause in patients aged <65 (n = 279), ≥65 (n = 228), and ≥75 (n = 69) years.

In the <65-aged subgroup, the median OS for those treated with trifluridine and tipiracil was 5.1 months compared to 3.2 months for those treated with placebo. The combination of trifluridine and tipiracil was also preferred over placebo for OS in the ≥65-aged subgroup (6.2 months vs 5.4 months, respectively) and the ≥75-aged subgroup (6.6 vs 5.4 months, respectively).

According to the study authors, the hazard ratios of PFS showed favorability of the combination regimen over placebo across all the subgroups.

The most common adverse events seen in the trifluridine and tipiracil group were neutropenia, nausea, anemia, and decreased appetite; adverse events were similar for younger and older patients.

Median treatment duration was longer among older patients, and cumulative trifluridine and tipiracil doses were slightly higher for the ≥65- and ≥75-aged subgroups. The median time to treatment discontinuation in the trifluridine and tipiracil group was 2.1 months versus 1.9 months in the placebo group (hazard ratio, 0.54; 95% confidence interval, 0.44-0.66).

“The results of this subgroup analysis show the efficacy and tolerability of [trifluridine and tipiracil] treatment regardless of age in patients with [metastatic gastric/GEJ cancers] who had received 2 or more prior treatments,” the researchers concluded.

Source:

Shitara K, Doi T, Hosaka H, et al. Efficacy and safety of trifluridine/tipiracil in older and younger patients with metastatic gastric or gastroesophageal junction cancer: Subgroup analysis of a randomized phase 3 study (TAGS). Gastric Cancer. 2022;25:586-597.doi:10.1007/s10120-021-01271-9.