4391 - TAGS: a phase 3, randomised, double-blind study of trifluridine/tipiracil (TAS-102) versus placebo in patients with refractory metastatic gastric cancer

Background

Trifluridine/tipiracil (FTD/TPI) demonstrated promising efficacy and was well tolerated in a Japanese phase 2 trial of pretreated patients (pts) with advanced gastric cancer. TAGS (NCT02500043) was conducted to confirm these findings.

Methods

This global phase 3 study enrolled pts aged ≥18 y with histologically confirmed, non-resectable metastatic gastric cancer (mGC), Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1, and ≥2 prior chemotherapy regimens. Pts were randomised 2:1 to receive FTD/TPI (35 mg/m² BID on days 1–5 and 8–12 of each 28-day cycle) or placebo, plus best supportive care.

Results

Between Feb 2016 and Jan 2018, 507 pts were randomised to receive FTD/TPI (n=337) or placebo (n=170). Baseline pt characteristics were balanced across treatment groups; 317 pts (63%) had received ≥3 lines of prior systemic therapy. At data cut-off (31 Mar 2018), median follow-up was 10.7 mo and the primary endpoint was met: the risk of death was lower with FTD/TPI vs placebo (HR 0.69; 95% CI 0.56–0.85; P=0.0003; median overall survival [OS] 5.7 vs 3.6 mo). Subgroup OS analyses favored FTD/TPI over placebo in most prespecified subgroups (eg, ethnicity, geographic region, ECOG PS, number of prior regimens). FTD/TPI vs placebo was associated with a lower risk of disease progression or death (HR 0.57; 95% CI 0.47–0.70; P<0.0001). Progression-free survival was longer with FTD/TPI vs placebo in all subgroups. Pts in the FTD/TPI group had a higher disease control rate (44% vs 14%; P<0.0001) and lower risk of ECOG PS deterioration to ≥2 (HR 0.69; 95% CI 0.56–0.85; P=0.0005). Grade ≥3 any-cause adverse events (AEs) were reported in 267/335 (80%) FTD/TPI-treated pts and 97/168 (58%) placebo-treated pts. Any-grade AEs led to dosing delay/dose reduction in 195 (58%) FTD/TPI-treated and 37 (22%) placebo-treated pts. Dosing delays were used more often than dose reduction to manage AEs. One treatment-related death was reported in each treatment group. No new safety signals were noted.

Conclusions

In this phase 3 study, FTD/TPI provided clinically meaningful and statistically significant prolongation in OS (31% reduction in risk of death) and was well tolerated in pts with heavily pretreated mGC.

Clinical trial identification

NCT02500043

Editorial Acknowledgement

Medical writing and editorial assistance were provided by Mark Palangio, Wendy Sacks, and Lilly Ostrovsky of Scientific Connexions, funded by Taiho Oncology, Inc.