Research in context
Evidence before this study
We searched PubMed without language restrictions on July 14, 2018, with the terms “advanced gastric cancer”, “metastatic gastric cancer”, “advanced gastroesophageal cancer”, and “metastatic gastroesophageal cancer” (and synonyms) combined with “later-line”, “third-line”, or “salvage therapy” for reports published between Jan 1, 2012, and Dec 31, 2015. As of June 30, 2015, when our study protocol was finalised, no third-line treatments had been approved globally for advanced or metastatic gastric cancer (although apatinib had been approved in China in 2014), and no international guidelines provided recommendations for such treatment.
Added value of this study
Treatment options are few for patients with heavily pretreated metastatic gastric cancer. To the best of our knowledge, ours is the first randomised, controlled trial with any approved treatment to be done in this population. Compared with placebo, trifluridine/tipiracil was associated with significant improvements in overall survival and had a manageable safety profile.
Implications of all the available evidence
Trifluridine/tipiracil could be a new treatment option for patients with heavily pretreated advanced gastric cancer after progression on, or intolerance to, two or more previous lines of chemotherapy, including a fluoropyrimidine, a platinum agent, a taxane or irinotecan (or both), and an anti-HER2 therapy (in patients with HER2-positive disease). In view of trifluridine/tipiracil's efficacy and tolerability, future research exploring the treatment in novel combination regimens could be warranted.