Evaluating trifluridine + tipiracil hydrochloride in a fixed combination (TAS-102) for the treatment of colorectal cancer

ABSTRACT

Introduction: Despite major progress in treating advanced colorectal cancer (CRC), prognosis in this population after progression on standard treatment remains dismal and the development of new drugs represents an unmet need. Historically, fluoropyrimidines have played a major role in the treatment of metastatic CRC. TAS-102, a novel combination of trifluridine and tipiracil hydrochloride, has demonstrated improvement in overall survival in the refractory CRC setting, with a safe toxicity profile.

Areas covered: A literature review of published clinical studies was performed. Herein, the authors review the pharmacological and clinical data of TAS-102 when used in metastatic CRC, both as a single agent as well as in novel combinations under investigation.

Expert opinion: The addition of TAS-102 to the therapeutic armamentarium of metastatic CRC is an encouraging breakthrough considering the demonstrated survival benefit and favorable tolerability profile. Combinations with other agents are under clinical investigation in different settings in an attempt to widen its use. To optimize treatment in today’s era of molecular oncology, efforts should be focused on understanding primary and secondary resistance mechanisms, along with the identification of potential biomarkers of response.

KEYWORDS:

• Biomarker
• colorectal cancer
• combination therapy
• RECOURSE
• refractory setting
• TAS-102
• trifluridine
• tipiracil hydrochloride

Box 1. Drug summary.

Acknowledgments

The authors thank Sarah McKenzie for her medical writing assistance.

Declaration of interest

J Tabernero has acted as a consultant or held an advisory role with Amgen, Bayer Healthcare, Boehringer Ingelheim, Celgene, Chugai Pharmaceutical Co., Ltd, Genentech, Eli Lilly and Company, Merck Sharp and Dohme, Merck Serono, Novartis, Roche, Sanofi, Symphogen, Taiho and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. One referee declares that they have served as a consultant for Taiho in the past while another declares that they have served as a scientific advisor for Taiho and Bayer Healthcare and have received research funding from both.

Additional information

Funding

This manuscript has not been funded.