Trifluridine/tipiracil versus placebo for third or later lines of treatment in metastatic gastric cancer: an exploratory subgroup analysis from the TAGS study.

Background: Metastatic gastric cancer and cancer of the esophagogastric junction (GC/EGJ) is an aggressive disease with poor prognosis. In the TAGS study, trifluridine/tipiracil (FTD/TPI) improved overall survival (OS) compared with placebo in heavily pre-treated patients. This unplanned, exploratory subgroup analysis of the TAGS study aimed to clarify outcomes when FTD/TPI was used as third-line (3L) treatment and fourth- or later-line (4L+) treatment.
Patients and Methods: Patients were divided into a 3L group (126 and 64 in FTD/TPI and placebo arms, respectively) and 4L+ group (211 and 106 in FTD/TPI and placebo arms, respectively). Endpoints included OS, progression-free survival (PFS), time to Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration to ≥2, and safety.
Results: Baseline characteristics were generally well balanced between FTD/TPI and placebo for 3L and 4L+ treatment. Median OS (mOS) for FTD/TPI versus placebo was: 6.8 versus 3.2 months {hazard ratio (HR) [95% confidence interval (CI)] = 0.68 (0.47-0.97), P = 0.0318} in the 3L group; and 5.2 versus 3.7 months [0.73 (0.55-0.95), P = 0.0192] in the 4L+ group. Median PFS for FTD/TPI versus placebo was 3.1 versus 1.9 months [0.54 (0.38-0.77), P = 0.0004] in the 3L group; and 1.9 versus 1.8 months [0.57 (0.44-0.74), P < 0.0001] in the 4L+ group. Time to deterioration of ECOG PS to ≥2 for FTD/TPI versus placebo was 4.8 versus 2.0 months [HR (95% CI) = 0.60 (0.42-0.86), P = 0.0049] in the 3L group; and 4.0 versus 2.5 months [0.75 (0.57-0.98), P = 0.0329] in the 4L+ group. The safety of FTD/TPI was consistent in all subgroups.
Conclusions: This analysis confirms the efficacy and safety of FTD/TPI in patients with GC/EGJ in third and later lines with a survival benefit that seems slightly superior in 3L treatment. When FTD/TPI is taken in 3L as recommended in the international guidelines, physicians can expect to provide patients with an mOS of 6.8 months.
Competing Interests: Disclosure JT: Consulting: Array BioPharma, AstraZeneca, Bayer, BeiGene, Biocartis, Boehringer Ingelheim, Chugai Pharma, Foundation Medicine, Genentech, Genmab, HalioDx, Halozyme, Imugene, Inflection Biosciences, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign, Rafael Pharmaceuticals, Roche, Roche Diagnostics, Sanofi, Seattle Genetics, Servier, Symphogen, Taiho Pharmaceutical, VCN Biosciences. KS: Consulting/honoraria/research funding: Abbvie, Astellas Pharma, BMS, Chugai Pharma, Daiichi Sankyo, GSK, Lilly, Mediscience Planning, MSD, Novartis, Ono Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, Taiho Pharmaceutical, Takeda, Yakult Pharmaceutical. AZ: Consulting/honoraria/expenses/research funding: Amgen, Baxter, Lilly, Merck Serono, MSD, Roche, Sanofi, Servier, Pierre Fabre, Havas Life, Alira Health, Zymeworks. TD: Consulting/honoraria/research funding: Abbvie, Amgen, Astellas Pharma, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Eisai, Lilly Japan, Merck Serono, MSD, Novartis, Oncolys BioPharma, Ono Pharmaceutical, Otsuka, Pfizer, Quintiles, Rakuten Medical, Sumitomo Dainippon Pharma, Taiho Pharmaceutical, Takeda. SL: Consulting/expenses/speaker: Amgen, BMS, Lilly, MSD Oncology, Roche, Sanofi-Aventis, Servier. EVC: Consulting/research funding: Amgen, Array BioPharma, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, BMS, Celgene, Daiichi Sankyo, GSK, Halozyme, Incyte, Ipsen, Lilly, MSD, Merck KGaA, Novartis, Pierre Fabre, Roche, Servier, Sirtex Medical, Taiho Pharmaceutical. LF: Consulting/honoraria/expenses/research funding: Celgene, Gilead Sciences, Lilly, MSD. DVTC: Consulting/honoraria/speaker: Amgen, Astella Pharma, BMS, Five Prime Therapeutics, Foundation Medicine, Genentech/Roche, Guardant Health, Lilly, Merck, Seattle Genetics, Taiho Pharmaceutical, Tempus. RF, SRM, and PA: Employees of Servier. H-TA: Consulting/honoraria/research funding: Bayer, BeiGene, Bicycle Therapeutics, Guardant Health, iOncologi, Merck KGaA, Roche, Sarah Cannon Research institute, Servier. MA: Consulting/expenses/speaker: Amgen, BMS, Lilly, MSD Oncology, Roche/Genentech, Servier. DHI: Consulting: Astellas Pharma, AstraZeneca, Bayer, BMS, Lilly/ImClone, Merck, Pieris Pharmaceuticals, Roche/Genentech, Taiho Pharmaceutical.
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