801PEfficacy and safety of trifluridine/tipiracil (FTD/TPI) in European patients with heavily pretreated metastatic gastric cancer (mGC): An analysis of the TAGS study

Abstract Background TAGS, a randomised, double-blind, phase III study, showed that FTD/TPI significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo in heavily pretreated mGC patients (pts) receiving best supportive care. The aim of this analysis was to evaluate the effects of FTP/TPI in the European subpopulation of TAGS. Methods TAGS enrolled pts with histologically confirmed, non-resectable mGC, Eastern Cooperative Oncology Group (ECOG) performance status 0/1, and ≥2 prior chemotherapy regimens. Pts were randomised 2:1 to FTD/TPI (35 mg/m2 BID on days 1–5 and 8–12 every 28 days) or placebo. Primary endpoint was OS. Secondary endpoints included PFS, time to deterioration (TTD) of ECOG and safety; 507 pts were randomised to FTD/TPI (n = 337) or placebo (n = 170). Median follow-up was 10.7 months. Results 277 pts (mean age 63.0 years; 75% male) were enrolled from 64 sites in Europe. Baseline characteristics were balanced between groups; 120 (67%) and 63 (65%) of pts in FTD/TPI and placebo groups had received ≥3 regimens of prior systemic therapy. FTP/TPI significantly prolonged OS (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.44-0.78), PFS (HR 0.46, 95% CI 0.35–0.61) and TTD to ECOG (HR 0.59, 95% CI 0.45–0.78; Table) compared with placebo. FTD/TPI had a predictable and manageable safety profile. Treatment-emergent adverse events (TEAEs) were reported in 172/180 (96%) FTD/TPI-treated and 92/97 (96%) placebo-treated pts. Efficacy and safety in European population of TAGS. Table . 801P FTD/TPI Placebo HR (95% CI) P-value (2-sided) (n = 180) (n = 97) Efficacy outcomes, median (95% CI) OS 5.45 (4.34– 6.21) 3.15 (2.43– 3.58) 0.59 (0.44– 0.78) 0.0002 PFS 1.94 (1.91– 2.50) 1.77 (1.74– 1.87) 0.46 (0.35– 0.61) TTD of ECOG 3.84 (2.89– 4.50) 2.10 (1.87– 2.53) 0.59 (0.45– 0.78) 0.0001 TEAEs, n (%) Any 172 (96.1) 92 (95.8) Serious 79 (44.1) 49 (51.0) Grade ≥3 143 (79.9) 62 (64.6) Treatment-related 140 (78.2) 55 (57.3) Leading to dose modification 107 (59.8) 26 (27.1) Leading to treatment discontinuation 24 (13.4) 19 (19.8) Leading to death 19 (10.6) 14 (14.6) Conclusions FTD/TPI was effective and well tolerated in European patients, consistent with the overall population of TAGS. Clinical trial identification NCT02500043. Editorial acknowledgement Simone Tait of Springer Healthcare Communications, funded by Institut de Recherches Internationales Servier. Legal entity responsible for the study Taiho Oncology and Taiho Pharmaceutical. Funding Taiho Oncology and Taiho Pharmaceutical. Disclosure M. Alsina: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Laboratoire Servier; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Merck. J. Tabernero: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy: Chugai Pharma; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Taiho pharmaceutical; Advisory / Consultancy: Takeda; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Array Biopharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BeiGene; Advisory / Consultancy: Servier. M. Squadroni: Research grant / Funding (self): Taiho Pharmaceutical; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Ipsen. T. Doi: Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Chugai Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Kyowa Hakko Kirin; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Daiichi Sankyo; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sumitomo Dainippon; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Taiho Pharmaceutical; Research grant / Funding (self): Novartis; Research grant / Funding (self): Merck Serono; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): MSD; Research grant / Funding (self): Janssen; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Takeda; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Lilly; Research grant / Funding (self): Celgene; Research grant / Funding (self): BMS; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Quintiles. C. Faustino: Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self): Astellas; Honoraria (self), Advisory / Consultancy: Servier. K. Shitara: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Astellas Pharma; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self): Yakult; Honoraria (institution): Dainippon Sumitomo Pharma; Honoraria (institution): Daiichi Sankyo; Honoraria (institution): Taiho Pharmaceutical; Honoraria (institution): Chugai Pharma; Honoraria (self), Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution): Medi Science. E. Van Cutsem: Research grant / Funding (self): Amgen; Research grant / Funding (self): Bayer; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Celgene; Research grant / Funding (self): Ipsen; Research grant / Funding (self): Lilly; Research grant / Funding (self): Merck; Research grant / Funding (self): Merck KgA; Research grant / Funding (self): Novartis; Research grant / Funding (self): Roche; Research grant / Funding (self): Sanofi; Research grant / Funding (self): Servier. N. Causse-Amellal: Full / Part-time employment: Laboratoire Servier. C. LEGER: Full / Part-time employment: Laboratoire Servier. D. Skanji: Full / Part-time employment: Laboratoire Servier. All other authors have declared no conflicts of interest.