Efficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors - Systematic Review

Sep 22, 2026

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A systematic review summarizes evidence from studies reporting clinical efficacy and safety for trifluridine/tipiracil (FTD/TPI) combined with other antineoplastic agents in advanced cancers. Searches through May 29, 2021 identified 1,378 publications, with 38 meeting selection criteria: 35 in metastatic colorectal cancer and 3 in other tumor types. Median overall survival and progression-free survival with FTD/TPI plus bevacizumab were reported for refractory disease, and combination therapy showed improved outcomes versus FTD/TPI monotherapy in comparative studies. Safety was generally acceptable, with neutropenia as the most frequent grade ≥3 adverse event and lower treatment discontinuation rates.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Implications for Practice

Introduction

Efficacy and Safety ofTrifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review Kohei Shitara,*, 1,2 Alfred Falcone,3 Marwan G. Fakih,4 Ben George,5 Raghav Sundar,6,7,8, Sandip Ranjan,9 Eric Van Cutsem10, 1 National Cancer Center Hospital East, Chiba, Japan 2Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan 3University of Pisa, Pisa, Italy 4City of Hope Comprehensive Cancer Center, Duarte, CA, USA 5Medical College of Wisconsin, Milwaukee, WI, USA 6Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Hospital, Singapore 7Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 8Yong Loo Lin School of Medicine, National University of Singapore, Singapore 9SmartAnalyst, an Ashfield Advisory Company, Gurugram, Haryana, India 10University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium * Corresponding author: Kohei Shitara, MD, National Cancer Center Hospital East, Kashiwa-Shi 277-8577, Japan, Tel: +81 4 7133 1111; Fax: +81 4 7134 6865; Email: [kshitara@east.ncc.go.jp](kshitara@east.ncc.go.jp) Abstract We performed a systematic literature review to identify and summarize data from studies reporting clinical efficacy and safety outcomes fortrifluridine/tipiracil (FTD/TPI) combined with other antineoplastic agents in advanced cancers, including metastatic colorectal cancer (mCRC) . We conducted a systematic search on May 29, 2021, for studies reporting one or more efficacy or safety outcome with FTD/TPI-containing combinations. Our search yielded 1378 publications, with 38 records meeting selection criteria: 35 studies of FTD/TPI-containing combinations in mCRC (31 studies second line or later) and 3 studies in other tumor types. FTD/TPI plus bevacizumab was extensively studied, including 19 studies in chemorefractory mCRC. Median overall survival ranged 8.6-14.4 months and median progression-free survival 3.7-6.8 months with FTD/TPI plus bevacizumab in refractory mCRC. Based on one randomized and several retrospective studies, FTD/TPI plus bevacizumab was associated with improved outcomes compared with FTD/TPI monotherapy. FTD/TPI combinations with chemotherapy or other targeted agents were reported in small early-phase studies; preliminary data indicated higher antitumor activity for certain combinations. Overall, no safety concerns existed with FTD/TPI combinations; most common grade ≥ 3 adverse event was neutropenia, ranging 5%-100% across all studies. In studies comparing FTD/TPI combinations with monotherapy, grade ≥ 3 neutropenia appeared more frequently with combinations (29%-67%) vs. monotherapy (5%-41%) . Discontinuation rates due to adverse events ranged 0%-11% for FTD/TPI plus bevacizumab and 0%-17% with other combinations. This systematic review supports feasibility and safety of FTD/TPI plus bevacizumab in refractory mCRC. Data on non-bevacizumab FTD/TPI combinations remain preliminary and need further validation. Key words: trifluridine; tipiracil; colorectal neoplasms; antineoplastic agents; antineoplastic drugs; review literature. Implications for Practice Trifluridine/tipiracil is approved as monotherapy in the treatment of metastatic colorectal and gastric cancers and has been explored in combinations with various antineoplastic combinations in clinical trials. This article provides an overview of the evidence for the activity and safety of these combinations across a variety of cancers. The data collected, summarized, and interpreted here will inform treatment of decision-making about the use of combination therapies that include trifluridine/tipiracil in the first- , second- , or third-line setting for the treatment gastrointestinal cancers across tumor types. Introduction Fluoropyrimidines, including 5-fluorouracil and capecitabine, alone or as part of combination regimens, have formed the mainstay in tre

FAQs

What did the systematic review evaluate about FTD/TPI combinations?

It identified and summarized clinical efficacy and safety outcomes for trifluridine/tipiracil (FTD/TPI) used with other antineoplastic agents in advanced cancers, including metastatic colorectal cancer.

How many studies met the selection criteria, and what cancer types were included?

Of 1,378 publications identified, 38 records met criteria: 35 studies in metastatic colorectal cancer and 3 studies in other tumor types.

What were the key safety findings across FTD/TPI combinations?

Overall, no safety concerns were reported. The most common grade ≥3 adverse event was neutropenia, with higher frequency in combination groups compared with FTD/TPI monotherapy in studies that made direct comparisons.

Sep 22, 2026

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