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Trifluridine/tipiracil provides the greatest clinical benefit when used in the third-line treatment of patients with metastatic gastric cancer

Previously, the pivotal phase III TAGS study established trifluridine/tipiracil (FTD/TPI) as an effective third- or later-line treatment option for patients with metastatic gastric or gastro-oesophageal junction cancer (GC/GEJC). An exploratory subgroup analysis of this trial, presented at ASCO GI 2021, now demonstrates that the survival benefit obtained from FTD/TPI is most pronounced when this drug is used in third-line. Similarly, also the benefit in terms of progression-free survival and deterioration to a worse performance status was most distinct in patients receiving FTD/TPI in third-line.


Metastatic GC/GEJC carries a poor prognosis, with a median OS with first-line treatment of approximately 1 year. In recent years, several effective salvage options have emerged for patients with disease progression in their first line treatment. In this respect, the TAGS study demonstrated an improved OS with FTD/TPI compared to placebo in metastatic GC/GEJC cancer patients who received at least 2 prior lines of therapy (median OS: 5.7 vs. 3.6 months). In an exploratory analysis of this trial, investigators looked into the clinical benefit obtained from FTD/TPI in function of the line of therapy in which the drug was used. For this analysis, patients were stratified into groups based on if they had received FTD/TPI or placebo in third line (N= 126 vs. 64), or if they had received FTD/TPI or placebo beyond third line (N= 211 vs. 106).

FTD/TPI associated with a median overall survival of 6.8 months in a 3rd line setting

With baseline characteristics well balanced between both groups, the median OS for patients receiving FTD/TPI or placebo in third line was 6.8 and 3.2 months, respectively (HR[95%CI]: 0.67[0.47-0.97], p= 0.0318). When used in the 3rd line setting FTD/TPI significantly prolonged the median PFS from 1.9 to 3.1 months, representing a 46% reduction in the risk of disease progression or death in favour of FTD/TPI  (HR[95%CI]: 0.54[0.38-0.77], p= 0.0004). In this third-line cohort, the time to deterioration of the ECOG performance status to ≥2 was reported at 4.8 months with FTD/TPI, which is significantly longer than the 2.0 months seen with placebo (HR[95%CI]: 0.60[0.42-0.86], p= 0.0049).

Also in later treatment lines (fourth line or beyond), FTD/TPI significantly outperformed placebo in terms of OS, PFS and time to ECOG PS deterioration (median OS: 5.2 vs. 3.7 months [HR: 0.72]; median PFS: 1.9 vs. 1.8 months [HR: 0.57]; median time to deterioration ECOG ≥2: 4.0 vs. 2.5 months [HR: 0.75]. However, this benefit was less pronounced than what was seen in patients receiving the drug in third line. The safety profile of FTD/TPI was consistent throughout all subgroup analyses.


This exploratory subgroup analysis confirms the efficacy and safety of FTD/TPI over placebo in the 3rd or later line treatment of patients with metastatic GC/GEJC, with a more pronounced clinical benefit in the 3rd line setting.


Tabernero J et al., Trifluridine/tipiracil outcomes in third- or later lines versus placebo in metastatic gastric cancer treatment: An exploratory subgroup analyses from the TAGS study. Presented at ASCO GI 2021; abstract 229.

Speaker Josep Tabernero

Josep Tabernero

Josep Tabernero, MD, PhD, Val d’Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain


See: Keyslides

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