预处理时使用血管内皮生长因子抑制剂对三氟尿苷/替匹嘧啶联合贝伐单抗治疗转移性结直肠癌患者安全性和疗效的影响。

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.

作者信息

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

机构信息

Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

出版信息

Int J Clin Oncol. 2025 Jul 21. doi: 10.1007/s10147-025-02831-0.

DOI:10.1007/s10147-025-02831-0

PMID:40690101

Abstract

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.

摘要

背景

血管内皮生长因子（VEGF）抑制剂预处理对转移性结直肠癌（mCRC）患者使用曲氟尿苷/替匹嘧啶（FTD/TPI）联合贝伐单抗（BEV）的临床疗效的影响尚不清楚。我们旨在研究这种影响。

方法

回顾性纳入接受FTD/TPI联合BEV治疗的mCRC患者。比较疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和不良事件（AE）。分别有73、50和33例患者接受氟尿嘧啶+亚叶酸钙+伊立替康（FOLFIRI）联合BEV、雷莫西尤单抗和阿柏西普治疗。

结果

各组间DCR和中位PFS/OS无显著差异（DCR：54.8%对56.0%对42.4%，P = 0.43；PFS：3.9对4.6对3.7个月，P = 0.45；OS：12.0对9.5对11.9个月，P = 0.28）。最常见的3-4级AE是中性粒细胞减少。3-4级AE的发生率在各组间无显著差异。FOLFIRI联合VEGF抑制剂治疗前有≥2级蛋白尿的患者在FTD/TPI联合BEV治疗期间≥2级蛋白尿的发生率显著高于无蛋白尿的患者。多因素分析显示，体能状态差（ECOG PS）和肝转移是PFS/OS短的独立预测因素（ECOG PS，PFS：P = 0.021，OS：P < 0.001；肝转移，PFS：P = 0.03，OS：P < 0.001），而1个月内发生3-4级中性粒细胞减少是PFS/OS长的预测因素（PFS：P = 0.047，OS：P = 0.03）。