The evidence supporting this protocol is provided by a phase III multicentre, international randomised trial (TAGS) involving 507 patients comparing trifluridine/tipiracil with placebo in patients with metastatic, non-resectable gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction). Patients had received at least two prior therapies, including fluoropyrimidine-, platinum-, and taxane- and/or irinotecan-based regimes. HER2-positive patients must have received prior HER2-targeted therapy if available.r
Between February 2016 and January 2018, 337 patients were randomised to receive trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1 to 5 and days 8 to 12 every 28 days and 170 patients were randomised to receive matching placebo.
The primary end point was overall survival (OS) and the secondary end points were progression-free survival (PFS), safety and tolerability, objective response, disease control rate (DCR), time to deterioration of ECOG status, and health-related quality of life.
After a median follow up of 10.7 months, the median OS was 5.7 months in the trifluridine/tipiracil group compared to 3.6 months in the placebo group (HR=0.69; 95% CI 0.56 to 0.85; p=0.00058). The 12 month survival rate was 21% versus 13% respectively. The median PFS was 2.0 months in the trifluridine/tipiracil group compared to 1.8 months in the placebo group (HR=0.57; 95% CI 0.47 to 0.70; p<0.0001). The 6 month PFS rate was 15% compared to 6% respectively. Objective responses were noted in 4% of the trifluridine/tipiracil group and 2% in the placebo group. DCR was 44% in the trifluridine/tipiracil group compared to 14% in the placebo group. The time to deterioration of ECOG status score to 2 or higher was significantly longer in the trifluridine/tipiracil group compared to the placebo group.r
Quality of life scores were largely stable in both groups.r
Kaplan-Meier curves for overall survival and progression-free survivalr
© Lancet Oncol 2018
Grade 3 or worse events occurred in 80% of patients in the trifluridine/tipiracil group compared to 58% in the placebo group. The most common grade 3/4 adverse events in the trifluridine/tipiracil group included neutropenia, anaemia and leucopenia.r
© Lancet Oncol 2018