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程序性死亡受体1(PD-1)阻断联合化疗及贝伐单抗治疗错配修复功能正常/微卫星稳定的结直肠癌肝转移

PD-1 blockade combined with chemotherapy and bevacizumab in DNA mismatch repair-proficient/microsatellite stable colorectal liver metastases.

作者信息

Men Qianqian, Duan Yinghua, Pei Fengyun, Yao Qijun, He Wan, Zhao Yandong, Shi Lishuo, Liu Guangjian, Huang Jun

机构信息

Graceland Medical Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Department of Traditional Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

J Gastrointest Oncol. 2024 Aug 31;15(4):1534-1544. doi: 10.21037/jgo-23-940. Epub 2024 Aug 12.


DOI:10.21037/jgo-23-940
PMID:39279968
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11399864/
Abstract

BACKGROUND: Single-agent immunotherapy is less effective in patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC). Whether pMMR/MSS mCRC patients benefit from combination immunotherapy remains unclear. This study aimed to evaluate the efficacy and safety of anti-programmed cell death protein 1 (PD-1) therapy combined with chemotherapy and bevacizumab in pMMR/MSS colorectal liver metastases (CRLM) patients. METHODS: A total of 12 patients with pMMR/MSS CRLM treated at The Sixth Affiliated Hospital of Sun Yat-sen University were enrolled. All patients were treated with at least 4 doses of PD-1 monoclonal antibody combined with chemotherapy and bevacizumab as neoadjuvant/adjuvant therapy. RESULTS: A total of 10 of the 12 patients received the combined therapies before primary tumor resection; the disease control rate (DCR) was 100% (10/10), and the objective response rate (ORR) was 70% (7/10). The ORR of liver metastases was 75% (9/12). Pathological complete response (pCR) was achieved in 1 primary tumor patient and 2 patients with hepatic lesions. A total of 5 patients underwent simultaneous resection of the primary tumor and liver metastases; 9 patients underwent microwave ablation for liver metastases. A total of 7 patients were assessed as having no evidence of disease (NED) with a median progression-free survival (PFS) interval of 9.2 (1.5-15.8) months after multimodality treatments for both primary and metastatic lesions. No severe immune-related adverse events (irAEs) and operational complications were observed. CONCLUSIONS: PD-1 blockade combined with chemotherapy and bevacizumab might be safe and effective for patients with pMMR/MSS CRLM. This treatment strategy might lead to better tumor regression and a higher chance of achieving NED.

摘要

背景:单药免疫疗法对DNA错配修复功能正常/微卫星稳定(pMMR/MSS)的转移性结直肠癌(mCRC)患者疗效较差。pMMR/MSS mCRC患者是否能从联合免疫疗法中获益仍不清楚。本研究旨在评估抗程序性细胞死亡蛋白1(PD-1)疗法联合化疗和贝伐单抗治疗pMMR/MSS结直肠癌肝转移(CRLM)患者的疗效和安全性。 方法:中山大学附属第六医院共纳入12例pMMR/MSS CRLM患者。所有患者均接受至少4剂PD-1单克隆抗体联合化疗和贝伐单抗作为新辅助/辅助治疗。 结果:12例患者中有10例在原发性肿瘤切除前接受了联合治疗;疾病控制率(DCR)为100%(10/10),客观缓解率(ORR)为70%(7/10)。肝转移灶的ORR为75%(9/12)。1例原发性肿瘤患者和2例肝转移灶患者达到病理完全缓解(pCR)。共有5例患者同时切除了原发性肿瘤和肝转移灶;9例患者接受了肝转移灶微波消融治疗。共有7例患者被评估为无疾病证据(NED),在对原发性和转移性病变进行多模式治疗后,中位无进展生存期(PFS)为9.2(1.5-15.8)个月。未观察到严重的免疫相关不良事件(irAE)和手术并发症。 结论:PD-1阻断联合化疗和贝伐单抗对pMMR/MSS CRLM患者可能是安全有效的。这种治疗策略可能导致更好的肿瘤退缩和更高的NED率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae56/11399864/89fc35c41913/jgo-15-04-1534-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae56/11399864/89fc35c41913/jgo-15-04-1534-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae56/11399864/89fc35c41913/jgo-15-04-1534-f1.jpg

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[1]
PD-1 blockade combined with chemotherapy and bevacizumab in DNA mismatch repair-proficient/microsatellite stable colorectal liver metastases.

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引用本文的文献

[1]
The neoadjuvant immunotherapy for non-metastatic mismatch repair-deficient colorectal cancer: a systematic review.

Front Immunol. 2025-5-1

本文引用的文献

[1]
Modified FOLFOX6 plus bevacizumab with and without nivolumab for first-line treatment of metastatic colorectal cancer: phase 2 results from the CheckMate 9X8 randomized clinical trial.

J Immunother Cancer. 2024-3-13

[2]
Neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, in mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer (PICC): a single-centre, parallel-group, non-comparative, randomised, phase 2 trial.

Lancet Gastroenterol Hepatol. 2022-1

[3]
Immune checkpoints and liver resection after neoadjuvant chemotherapy including bevacizumab in patients with microsatellite-stable colorectal liver metastases.

HPB (Oxford). 2022-1

[4]
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

CA Cancer J Clin. 2021-5

[5]
Old Player-New Tricks: Non Angiogenic Effects of the VEGF/VEGFR Pathway in Cancer.

Cancers (Basel). 2020-10-27

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Phase II study on first-line treatment of NIVolumab in combination with folfoxiri/bevacizumab in patients with Advanced COloRectal cancer RAS or BRAF mutated - NIVACOR trial (GOIRC-03-2018).

BMC Cancer. 2020-8-31

[7]
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Oncologist. 2020-8

[8]
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J Clin Oncol. 2020-6-20

[9]
Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers.

Nat Med. 2020-4-6

[10]
PD-1 blockade in neoadjuvant setting of DNA mismatch repair-deficient/microsatellite instability-high colorectal cancer.

Oncoimmunology. 2020-1-22

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