Trifluridine/tipiracil with or without bevacizumab in microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: A retrospective observational study

作者：Hiroko Hasegawa, Rin Inamoto, Keiji Sugiyama, Naoki Izawa, Seiichiro Mitani, Takeshi Kawakami, Satoshi Yuki, Hidekazu Hirano, Saori Mishima, Tetsutaro Hamano, Toshiki Masuishi · 发表于：Therapeutic Advances in Medical Oncology · 年份：2026 · DOI：10.1177/17588359261476046 · 研究领域：Genetic factors in colorectal cancer、Colorectal Cancer Treatments and Studies、Ferroptosis and cancer prognosis

Background Patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) have been reported to exhibit resistance to various cytotoxic agents, including fluorouracil. A preclinical study showed that trifluridine, a key active component of FTD/TPI, retained antitumor activity in 5-FU-refractory dMMR CRC cell lines. However, the efficacy of trifluridine/tipiracil (FTD/TPI), with or without bevacizumab, in patients with MSI-H/dMMR mCRC remains poorly understood. Objectives This study aimed to evaluate the clinical efficacy and safety of FTD/TPI, with or without bevacizumab, specifically in patients with MSI-H/dMMR mCRC. Design A retrospective, multicenter observational study was conducted across 10 hospitals in Japan. Methods We identified patients with MSI-H/dMMR mCRC treated with FTD/TPI as second- or later-line therapy between June 2012 and January 2023. All eligible patients were divided into two groups: FTD/TPI monotherapy (FT group) and FTD/TPI combined with bevacizumab (FTB group); the safety and efficacy of the two groups were compared. Whole-exome sequencing (WES) was performed on available samples to explore genomic features associated with treatment response of FTD/TPI. Results The objective response rate (ORR) was 16.7% (95% confidence interval [CI], 3.6–41.4); median progression-free survival (PFS) was 5.5 months, and median overall survival (OS) was 11.8 months in the overall cohort. Although the median PFS...