ArticleTherapeutic advances in medical oncology2026
Trifluridine/tipiracil with or without bevacizumab in microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: A retrospective observational study.
Article in Therapeutic advances in medical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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 was similar between the two groups (5.6 months in the FTB group and 5.2 months in the FT group, Conclusions: FTD/TPI, with or without bevacizumab, demonstrated favorable antitumor activity in patients with MSI-H/dMMR mCRC. These findings suggest that FTD/TPI-based treatment may represent a potentially useful treatment option for this rare population, although further studies are warranted.
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