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一项真实世界研究:转移性结直肠癌的三线治疗方案

A real-world study: third-line treatment options for metastatic colorectal cancer.

作者信息

Wu Chen, Li Shuai, Hou Xinfang

机构信息

Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

出版信息

Front Oncol. 2024 Dec 2;14:1480704. doi: 10.3389/fonc.2024.1480704. eCollection 2024.

Abstract

BACKGROUND

Numerous third-line treatment options exist for colorectal cancer. This study aims to assess the efficacy and safety of third-line therapies, including TKIs (fruquintinib, regorafenib) combined with PD-1 inhibitors, and trifluridine/tipiracil combined with bevacizumab, in patients with refractory microsatellite stable metastatic colorectal cancer who have progressed or are intolerant following standard first- and second-line treatments.

MATERIALS AND METHODS

This retrospective analysis collected data from patients with microsatellite stable advanced colorectal adenocarcinoma, diagnosed through histopathology and treated at Henan Provincial Cancer Hospital from May 2019 to April 2023. We compared the efficacy and safety of fruquintinib combined with PD-1 inhibitors, regorafenib combined with PD-1 inhibitors, and trifluridine/tipiracil combined with bevacizumab.

RESULTS

Among 60 eligible patients with refractory microsatellite stable metastatic colorectal adenocarcinoma, 29 (48.3%) received fruquintinib combined with PD-1 inhibitors, 15 (25%) received regorafenib combined with PD-1 inhibitors, and 16 (26.7%) received trifluridine/tipiracil combined with bevacizumab. The average follow-up period was 12.6 months (ranging from 2.3 to 37.6 months). After third-line treatment, the overall objective response rate (ORR) was 8.6%, and the disease control rate (DCR) was 78.6%. The median overall survival (OS) for the regorafenib, fruquintinib, and trifluridine/tipiracil groups was 19.2 months, 14.0 months, and 16.2 months, respectively, with no statistically significant differences observed. However, there were statistically significant differences in progression-free survival (PFS); the median PFS for the regorafenib group was 6.3 months, for the fruquintinib group was 4.2 months, and for the trifluridine/tipiracil group was 5.4 months. Pairwise comparisons indicated that the PFS for the regorafenib group was similar to that for the trifluridine/tipiracil group, both of which were superior to the fruquintinib group. Cox univariate regression analysis revealed that the presence of liver and peritoneal metastases was associated with PFS in third-line treatment.

CONCLUSION

In the third-line treatment of colorectal cancer, regorafenib combined with PD-1 inhibitors and trifluridine/tipiracil combined with bevacizumab showed superiority over fruquintinib combined with PD-1 inhibitors in terms of PFS, but no statistically significant difference in OS was noted among the three groups.

摘要

背景

结直肠癌存在多种三线治疗方案。本研究旨在评估三线治疗方案的疗效和安全性,这些方案包括酪氨酸激酶抑制剂(TKI,呋喹替尼、瑞戈非尼)联合程序性死亡受体1(PD-1)抑制剂,以及曲氟尿苷/替匹嘧啶联合贝伐单抗,用于标准一线和二线治疗后进展或不耐受的难治性微卫星稳定型转移性结直肠癌患者。

材料与方法

本回顾性分析收集了2019年5月至2023年4月在河南省肿瘤医院接受治疗、经组织病理学诊断为微卫星稳定型晚期结直肠腺癌患者的数据。我们比较了呋喹替尼联合PD-1抑制剂、瑞戈非尼联合PD-1抑制剂以及曲氟尿苷/替匹嘧啶联合贝伐单抗的疗效和安全性。

结果

在60例符合条件的难治性微卫星稳定型转移性结直肠腺癌患者中,29例(48.3%)接受了呋喹替尼联合PD-1抑制剂治疗,15例(25%)接受了瑞戈非尼联合PD-1抑制剂治疗,16例(26.7%)接受了曲氟尿苷/替匹嘧啶联合贝伐单抗治疗。平均随访期为12.6个月(范围为2.3至37.6个月)。三线治疗后,总体客观缓解率(ORR)为8.6%,疾病控制率(DCR)为78.6%。瑞戈非尼组、呋喹替尼组和曲氟尿苷/替匹嘧啶组的中位总生存期(OS)分别为19.2个月、14.0个月和16.2个月,未观察到统计学显著差异。然而,无进展生存期(PFS)存在统计学显著差异;瑞戈非尼组的中位PFS为6.3个月,呋喹替尼组为4.2个月,曲氟尿苷/替匹嘧啶组为5.4个月。两两比较表明,瑞戈非尼组的PFS与曲氟尿苷/替匹嘧啶组相似,两者均优于呋喹替尼组。Cox单因素回归分析显示,肝转移和腹膜转移的存在与三线治疗的PFS相关。

结论

在结直肠癌的三线治疗中,瑞戈非尼联合PD-1抑制剂以及曲氟尿苷/替匹嘧啶联合贝伐单抗在PFS方面优于呋喹替尼联合PD-1抑制剂,但三组在OS方面未观察到统计学显著差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70c9/11648419/4843629c0018/fonc-14-1480704-g001.jpg

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