Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer

被引：177

作者：

Li, Song ^{[1
]}

Yu, Wenbin ^{[2
]}

Xie, Fei ^{[3
]}

Luo, Haitao ^{[4
]}

Liu, Zhimin ^{[5
]}

Lv, Weiwei ^{[6
]}

Shi, Duanbo ^{[7
]}

Yu, Dexin ^{[6
]}

Gao, Peng ^{[7
]}

Chen, Cheng ^{[2
]}

Wei, Meng ^{[2
]}

Zhou, Wenhao ^{[4
]}

Wang, Jiaqian ^{[4
]}

Zhao, Zhikun ^{[4
]}

Dai, Xin ^{[8
]}

Xu, Qian ^{[1
]}

Zhang, Xue ^{[1
]}

Huang, Miao ^{[1
]}

Huang, Kai ^{[1
]}

Wang, Jian ^{[1
]}

Li, Jisheng ^{[1
]}

Sheng, Lei ^{[2
]}

Liu, Lian ^{[1
]}

机构：

[1] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Med Oncol, Jinan 250012, Shandong, Peoples R China

[2] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Gen Surg, Jinan 250012, Shandong, Peoples R China

[3] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Pharm, Jinan 250012, Shandong, Peoples R China

[4] Shenzhen Yucebio Technol Co Ltd, Shenzhen 518000, Guangdong, Peoples R China

[5] Zibo Municipal Cent Hosp, Binzhou Med Coll, Dept Gen Surg, Zibo 255036, Shandong, Peoples R China

[6] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Radiol, Jinan 250012, Shandong, Peoples R China

[7] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Pathol, Jinan 250012, Shandong, Peoples R China

[8] Shandong Prov Hosp Tradit Chinese Med, Dept Med Oncol, Jinan 250012, Peoples R China

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

基金：

中国国家自然科学基金;

关键词：

GASTROESOPHAGEAL JUNCTION; PERIOPERATIVE CHEMOTHERAPY; OPEN-LABEL; PHASE-II; DOUBLE-BLIND; SINGLE-ARM; ADENOCARCINOMA; MULTICENTER; TRIAL; PEMBROLIZUMAB;

D O I：

10.1038/s41467-022-35431-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 +/- oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers. Immune checkpoint inhibitors and antiangiogenic agents have shown some activity in patients with late-stage gastric cancer. Here the authors report the results of a phase II trial of neoadjuvant anti-PD1 (camrelizumab), antiangiogenic agent (apatinib), and chemotherapy (S-1 +/- Oxaliplatin) in stage T4a/bN + M0 gastric cancer patients.

引用

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