Trifluridine/tipiracil for the treatment of metastatic gastric cancer

ABSTRACT

Introduction: Trifluridine/tipiracil is a novel oral cytotoxic chemotherapy consisting of a thymidine-based nucleoside analog, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil. Trifluridine/tipiracil was approved for the treatment of metastatic colorectal cancer refractory to standard therapies. A phase II trial in Japan demonstrated that this therapy has antitumor activity and is tolerated by patients with advanced gastric cancer (AGC); as a result, the phase III TAGS trial (Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer) was initiated.

Area covered: Trifluridine/tipiracil has proved effective for heavily pretreated AGC and has thus been approved for use in the United States in February 2019, Japan in August 2019 and the European Union in September 2019. Detail of the phase III TAGS trial is discussed in this review.

Expert opinion: Trifluridine/tipiracil after at least two previous courses of systemic chemotherapy improved rates of survival of gastric cancer; thus it has become one of the treatment options in affected patients. Currently, several clinical trials of trifluridine/tipiracil in combination with other anticancer agents such as ramucirumab (an anti-vascular endothelial growth factor receptor 2 monoclonal antibody) for patients with AGC are ongoing.

KEYWORDS:

• Trifluridine/tipiracil
• gastric cancer
• clinical trials
• combination therapies
• optimal selection

Article highlights

• Trifluridine/tipiracil, a novel oral cytotoxic chemotherapy, has proved effective for heavily pretreated AGC.

• Trifluridine/tipiracil was associated with significantly improved overall survival in comparison with placebo (5.7 vs. 3.6 months) in patients with AGC who had received at least two previous chemotherapy. Progression-free survival and disease control rate were also better, in comparison with placebo.

• Major adverse effects of trifluridine/tipiracil in the TAGS study include myelosuppressive and gastrointestinal events; this finding is consistent with those in the phase III RECOURSE study in patients with mCRC and in the phase II EPOC1201 study in Japanese patients with AGC.

• Currently, the use of trifluridine/tipiracil in combination with other anticancer agents for patients with AGC is being investigated.

Declaration of interest

A. Kawazoe reports research funding from Ono, Sumitomo Dainippon, and Taiho. K. Shitara reports paid consulting or advisory roles for Astellas, Lilly, Bristol-Myers Squibb, Takeda, Pfizer, Ono, and MSD; honoraria from Novartis, AbbVie, and Yakult; and research funding from Astellas, Lilly, Ono, Sumitomo Dainippon, Daiichi Sankyo, Taiho, Chugai, MSD and Medi Science. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.