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Background <p>The effect of vascular endothelial growth factor (VEGF) inhibitor pretreatment on clinical outcomes of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) in patients with metastatic colorectal cancer (mCRC) remains unclear. We aimed to investigate this effect.</p> Methods <p>Patients with mCRC treated with FTD/TPI plus BEV were retrospectively enrolled. Disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared. In total, 73, 50, and 33 patients were treated with fluorouracil+levofolinate calcium+irinotecan (FOLFIRI) plus BEV, ramucirumab, and aflibercept, respectively.</p> Results <p>The DCR and median PFS/OS did not significantly differ among the groups (DCR: 54.8% vs. 56.0% vs. 42.4%, <i>P</i>&#xa0;=&#xa0;0.43; PFS: 3.9 vs. 4.6 vs. 3.7 months, <i>P</i>&#xa0;=&#xa0;0.45; OS: 12.0 vs. 9.5 vs. 11.9 months, <i>P</i>&#xa0;=&#xa0;0.28). The most common grade 3–4 AE was neutropenia. The incidence of grade 3–4 AEs did not significantly differ among the groups. The frequency of grade ≥2 proteinuria during FTD/TPI plus BEV treatment was significantly higher in patients with grade ≥2 proteinuria before FOLFIRI plus VEGF inhibitor use than in those without proteinuria. Multivariate analysis revealed poor performance status (ECOG PS) and liver metastasis as independent predictors of short PFS/OS (ECOG PS, PFS: <i>P</i>&#xa0;=&#xa0;0.021, OS: <i>P</i>&#xa0;&lt;&#xa0;0.001; liver metastasis, PFS: <i>P</i>&#xa0;=&#xa0;0.03, OS: <i>P</i>&#xa0;&lt;&#xa0;0.001) and grade 3–4 neutropenia in a month as a predictor of long PFS/OS (PFS: <i>P</i>&#xa0;=&#xa0;0.047, OS: <i>P</i>&#xa0;=&#xa0;0.03).</p> Conclusion <p>Different pretreatment VEGF inhibitors did not affect the efficacy and safety of FTD/TPI plus BEV.</p>

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Effect of pretreatment vascular endothelial growth factor inhibitor use on the safety and efficacy of trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer

  • 期刊论文

  • 发表日期：

    2025年7月21日

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  • Koshiro Fukuda,
  • Hiroki Osumi,
  • Akira Ooki,
  • Daisaku Kamiimabeppu,
  • Shohei Udagawa,
  • Shota Fukuoka,
  • Mariko Ogura,
  • Takeru Wakatsuki,
  • Keisho Chin,
  • Mitsuhiro Fujishiro,
  • Kensei Yamaguchi,
  • Eiji Shinozaki

摘要

Background

The effect of vascular endothelial growth factor (VEGF) inhibitor pretreatment on clinical outcomes of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) in patients with metastatic colorectal cancer (mCRC) remains unclear. We aimed to investigate this effect.

Methods

Patients with mCRC treated with FTD/TPI plus BEV were retrospectively enrolled. Disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared. In total, 73, 50, and 33 patients were treated with fluorouracil+levofolinate calcium+irinotecan (FOLFIRI) plus BEV, ramucirumab, and aflibercept, respectively.

Results

The DCR and median PFS/OS did not significantly differ among the groups (DCR: 54.8% vs. 56.0% vs. 42.4%, P = 0.43; PFS: 3.9 vs. 4.6 vs. 3.7 months, P = 0.45; OS: 12.0 vs. 9.5 vs. 11.9 months, P = 0.28). The most common grade 3–4 AE was neutropenia. The incidence of grade 3–4 AEs did not significantly differ among the groups. The frequency of grade ≥2 proteinuria during FTD/TPI plus BEV treatment was significantly higher in patients with grade ≥2 proteinuria before FOLFIRI plus VEGF inhibitor use than in those without proteinuria. Multivariate analysis revealed poor performance status (ECOG PS) and liver metastasis as independent predictors of short PFS/OS (ECOG PS, PFS: P = 0.021, OS: P < 0.001; liver metastasis, PFS: P = 0.03, OS: P < 0.001) and grade 3–4 neutropenia in a month as a predictor of long PFS/OS (PFS: P = 0.047, OS: P = 0.03).

Conclusion

Different pretreatment VEGF inhibitors did not affect the efficacy and safety of FTD/TPI plus BEV.