Effects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS)

BACKGROUND: In the phase III TAGS trial, trifluridine/tipiracil showed survival benefit versus placebo in patients with metastatic gastric/gastroesophageal junction cancer and ≥ 2 prior chemotherapies. This post hoc exploratory analysis assessed the impact of prior therapy type on outcomes. METHODS: Based on prior treatment, patients in TAGS (N = 507) were categorized into overlapping subgroups: ramucirumab ± other agents (n = 169), no ramucirumab (n = 338), paclitaxel but no ramucirumab (n = 136), ramucirumab + paclitaxel sequentially or in combination (n = 154), neither paclitaxel nor ramucirumab (n = 202), irinotecan (n = 281), and no irinotecan (n = 226). Overall and progression-free survival, time to Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, and safety were assessed. RESULTS: Baseline characteristics and prior therapy patterns were generally well balanced between trifluridine/tipiracil and placebo arms across subgroups. Trifluridine/tipiracil was associated with survival benefits versus placebo regardless of prior treatment: across subgroups, median overall survival was 4.6–6.1 versus 3.0–3.8 months (hazard ratios, 0.47–0.88), median progression-free survival was 1.9–2.3 versus 1.7–1.8 months (hazard ratios, 0.49–0.67), and median time to ECOG PS ≥ 2 was 4.0–4.7 versus 1.9–2.5 months (hazard ratios, 0.56–0.88). Among trifluridine/tipiracil-randomized patients, median overall and progression-free survival trended longer in those who had not received ramucirumab, paclitaxel and ramucirumab, or irinotecan (6.0–6.1 and 2.1–2.3 months, respectively) than in those who previously received these agents (4.6–5.7 and 1.9 months). The trifluridine/tipiracil safety profile was consistent across subgroups, with similar overall incidences of grade ≥ 3 adverse events. Minor variations in hematologic toxicities were noted. CONCLUSIONS: In TAGS, third- or later-line trifluridine/tipiracil treatment demonstrated overall and progression-free survival and functioning benefits versus placebo and a consistent safety profile in patients with metastatic gastric/gastroesophageal junction cancer, regardless of prior treatment type. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT02500043. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-023-04813-z.