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抗PD-1抗体联合小分子抗血管生成药物及化疗在胃癌腹膜转移中的疗效与安全性:一项多中心真实世界研究

Efficacy and safety of anti-PD-1 antibodies plus small molecule anti-angiogenic drugs and chemotherapy in gastric cancer peritoneal metastasis: a multicenter real-world study.

作者信息

Guo Fen, Wang Deqiang, Zhang Luyao, Fang Yueyu, Shi Jianming, Wang Guoqiang, Yu Mingyang, Feng Yuxin, Wang Liyu, Feng Ying, Chen XiaoFeng

机构信息

Department of Oncology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, No.16 Baita West Road, Suzhou, Jiangsu Province, 215000, China.

Gusu School, Nanjing Medical University, No.458 Shizi Street, Suzhou, Jiangsu Province, 215000, China.

出版信息

BMC Cancer. 2025 Jul 1;25(1):1028. doi: 10.1186/s12885-025-14426-z.


DOI:10.1186/s12885-025-14426-z
PMID:40597880
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12211162/
Abstract

BACKGROUND: Immunotherapy combined with chemotherapy has emerged as the first-line standard treatment for advanced gastric cancer. However, obvious survival benefits in patients with peritoneal metastatic gastric cancer remain elusive. The combination of anti-angiogenic agents and immunotherapy has shown synergistic effects. However, currently there are no relevant reports on the efficacy and safety of immunotherapy combined with anti-angiogenic agents and chemotherapy in patients with gastric cancer peritoneal metastatic. METHODS: We conducted a multicenter, retrospective clinical study in four independent healthcare facilities, enrolling advanced gastric cancer patients with peritoneal metastatic who received immunotherapy in combination with anti-angiogenic agents and chemotherapy between January 2020 and March 2023. All patients were treated with triple combination regimen for at least two and up to eight cycles before being adjusted for immunotherapy and targeted therapy. This study observed overall survival (OS) and time to treatment failure (TTF), as well as an exploratory analysis of the impact of ascites and peritoneal metastases on the prognosis of all patients. RESULTS: This study enrolled 30 eligible patients in the final analysis cohort. The median TTF and OS were 7.03 months [95% confidence interval (CI), 4.17-9.89] and 13.33 months (95% CI: 10.96-15.71), respectively. The 6-month and 12-month OS rates were 83.0% and 53.0%, respectively. The objective response rate (ORR) was 58.3%, and the disease control rate (DCR) was 83.3% in 12 patients who were evaluated for response with at least one measurable lesion. Exploratory subgroup analysis revealed that the median TTF and OS in the subgroup without ascites were significantly better than those in the subgroup with ascites, with a median TTF of 9.03 vs. 4.63 months (χ = 8.579, P = 0.003), and median OS of 17.83 vs. 11.87 months (χ = 6.155, P = 0.013). Conversely, the extent of peritoneal metastasis had little effect on TTF and OS. The common adverse reactions were leukopenia (46.67%), neutropenia (43.33%), fatigue (36.67%), anemia (36.67%), decreased appetite (36.67%), thrombocytopenia (33.33%), and hypertension (33.33%). No new safety signals were observed. CONCLUSIONS: The combination of immunotherapy, anti-angiogenic agents, and chemotherapy demonstrated therapeutic potential with a manageable safety profile in patients with peritoneal metastatic gastric cancer. These findings should be interpreted cautiously due to the inherent limitations of retrospective analyses and need to be validated through prospective randomized controlled trials to establish clinical efficacy and optimize patient selection criteria.

摘要

背景:免疫疗法联合化疗已成为晚期胃癌的一线标准治疗方案。然而,腹膜转移性胃癌患者的明显生存获益仍不明确。抗血管生成药物与免疫疗法联合已显示出协同作用。然而,目前尚无关于免疫疗法联合抗血管生成药物及化疗在胃癌腹膜转移患者中的疗效和安全性的相关报道。 方法:我们在四个独立的医疗机构进行了一项多中心回顾性临床研究,纳入2020年1月至2023年3月期间接受免疫疗法联合抗血管生成药物及化疗的晚期腹膜转移性胃癌患者。所有患者在接受免疫疗法和靶向治疗调整前,均接受三联联合方案治疗至少两个周期,最多八个周期。本研究观察总生存期(OS)和治疗失败时间(TTF),并对腹水和腹膜转移对所有患者预后的影响进行探索性分析。 结果:本研究最终分析队列纳入30例符合条件的患者。中位TTF和OS分别为7.03个月[95%置信区间(CI),4.17 - 9.89]和13.33个月(95% CI:10.96 - 15.71)。6个月和12个月的OS率分别为83.0%和53.0%。在12例有至少一个可测量病灶进行疗效评估的患者中,客观缓解率(ORR)为58.3%,疾病控制率(DCR)为83.3%。探索性亚组分析显示,无腹水亚组的中位TTF和OS显著优于有腹水亚组,中位TTF分别为9.03个月对4.63个月(χ = 8.579,P = 0.003),中位OS分别为17.83个月对11.87个月(χ = 6.155,P = 0.013)。相反,腹膜转移程度对TTF和OS影响较小。常见不良反应为白细胞减少(46.67%)、中性粒细胞减少(43.33%)、疲劳(36.67%)、贫血(36.67%)、食欲下降(36.67%)、血小板减少(33.33%)和高血压(33.33%)。未观察到新的安全信号。 结论:免疫疗法、抗血管生成药物和化疗联合在腹膜转移性胃癌患者中显示出治疗潜力,且安全性可控。由于回顾性分析的固有局限性,这些发现应谨慎解读,需要通过前瞻性随机对照试验进行验证,以确立临床疗效并优化患者选择标准。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfa9/12211162/310bb9b2af00/12885_2025_14426_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfa9/12211162/035a80efe39d/12885_2025_14426_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfa9/12211162/f842501ef57e/12885_2025_14426_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfa9/12211162/020d26580fd2/12885_2025_14426_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfa9/12211162/310bb9b2af00/12885_2025_14426_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfa9/12211162/035a80efe39d/12885_2025_14426_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfa9/12211162/f842501ef57e/12885_2025_14426_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfa9/12211162/020d26580fd2/12885_2025_14426_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfa9/12211162/310bb9b2af00/12885_2025_14426_Fig4_HTML.jpg

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本文引用的文献

[1]
Co-delivery of axitinib and PD-L1 siRNA for the synergism of vascular normalization and immune checkpoint inhibition to boost anticancer immunity.

J Nanobiotechnology. 2025-3-10

[2]
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Front Immunol. 2024-12-3

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Clin Transl Med. 2024-10

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BMJ. 2024-5-28

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Cell Death Dis. 2024-3-15

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