Effects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS). J Cancer Res Clin Oncol 2023 Sep;149(11):9361-9374
Date
05/22/2023Pubmed ID
37213030Pubmed Central ID
PMC10374776DOI
10.1007/s00432-023-04813-zScopus ID
2-s2.0-85160105116 (requires institutional sign-in at Scopus site)Abstract
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.
Author List
Shitara K, George B, Taieb J, Sundar R, Fakih MG, Makris L, Benhadji KA, Ghidini MAuthor
Ben George MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antineoplastic Combined Chemotherapy ProtocolsColorectal Neoplasms
Drug Combinations
Esophagogastric Junction
Humans
Paclitaxel
Pyrrolidines
Stomach Neoplasms
Trifluridine
