免疫治疗在胃癌的围手术期及转化治疗中的应用和挑战

doi:10.19401/j.cnki.1007-3639.2024.03.003

摘要/Abstract

摘要：

胃癌是中国常见的消化系统恶性肿瘤之一，进展期及晚期患者占比高，围手术期治疗方案的选择始终是临床上的难点。对多数局部进展期胃癌，围手术期治疗模式相较于标准根治术联合术后辅助化疗的模式，也许可以进一步改善患者生存，但传统化疗方案的疗效已达到平台期，传统分子靶向治疗进展相对缓慢，近年来，随着免疫治疗在晚期胃癌治疗中的地位不断提升，越来越多的临床研究表明，免疫治疗在围手术期胃癌患者中也可以取得较好的疗效。本文就近年来免疫治疗在胃癌围手术期中应用的研究进展进行述评。

关键词: 胃癌, 免疫治疗, 临床试验, 新辅助治疗, 转化治疗

Abstract:

Gastric cancer is one of the common malignant tumors of digestive system in our country. The proportion of patients in advanced and late stage is large, and the choice of perioperative treatment program is always difficult in clinic. For most locally advanced gastric cancer, compared with standard radical surgery combined with postoperative adjuvant chemotherapy, perioperative treatment mode may further improve the survival of patients. However, the efficacy of conventional chemotherapy regimen has reached a plateau, while the progress of traditional molecular targeted therapy is relatively slow. In recent years, with the increasing role of immunotherapy in the treatment of advanced gastric cancer, more and more clinical studies have shown that immunotherapy can also achieve better efficacy in perioperative gastric cancer patients. This article reviewed the research progress of immunotherapy in perioperative gastric cancer in recent years.

Key words: Gastric cancer, Immunotherapy, Clinical trials, Neoadjuvant therapy, Conversion therapy

中图分类号:

R735.2

薛驰, 高鹏, 朱志, 王振宁. 免疫治疗在胃癌的围手术期及转化治疗中的应用和挑战[J]. 中国癌症杂志, 2024, 34(3): 259-267.

XUE Chi, GAO Peng, ZHU Zhi, WANG Zhenning. Application and challenge of immunotherapy in perioperative therapy of gastric cancer[J]. China Oncology, 2024, 34(3): 259-267.

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Treatment	Clinical trial	Medication regimen	Cycle	Stage	Content
ICI monotherapy	JapicCTI-183895	Nivolumab	2 cycles	Ⅰ	pCR: 1 (3.2%); MPR: 5 (16.1%)
The combination of neoadjuvant chemotherapy and ICI	GERCOR NEONIPIGA	Nivolumab+ipilimumab pre-operative; Nivolumab post-operative	6 cycles pre-operative; 9 cycles post-operative	Ⅱ	pCR rate: 58.6% (17/32); TRG 0-1: 73% (21/32)
	PANDA	Atezolizumab; Atezolizumab+docetaxel	1 cycles Atezolizumab; 4 cycles atezolizumab+docetaxel	Ⅱ	MPR rate: 70% (14/20); pCR rate: 45% (9/20)
	INFINITY	Tremelimumab+durvalumab	3 cycles tremelimumab (300 mg)+durvalumab (1500 mg), q4w	Ⅱ	pCR rate: 60% (9/15); MPR rate: 80% (12/15)
The combination of perioperative treatment and ICI	NEOSUMMIT-01	Toripalimab +SOX/XELOX	3 cycles pre-operative; 5 cycles post-operative	Ⅱ	TRG 0-1: 44.4%
	DANTE	Atezolizumab+FLOT	4 cycles atezolizumab +FLOT pre-operative and post-operative; 4 cycles atezolizumab vs FLOT post-operative	Ⅱ/Ⅲ	TRG 0-1: 24.0%
	KEYNOTE-585	Pembrolizumab+XP/FP/FLOT vs placebo+XP/FP/FLOT	4 cycles pre-operative; 3+11 cycles post-operative	Ⅲ	pCR rate: 12.9% vs 2.0%; mOS: 60.7 months vs 58.0 months; mPFS: 44.4 months vs 25.3 months

Patient classification	Clinical trial	Patient population	Medication regimens	Stage	Content
PD-L1 CPS≥5	CheckMate-649	Advanced or metastatic HER2- gastric or gastro-oesophageal junction adenocarcinoma	Nivolumab+XELOX/FOLFOX vs XELOX/FOLFOX	Ⅲ	mOS: 14.4 months vs 11.1 months; mPFS: 7.7 months vs 6.05 months; ORR: 60% vs 45%
	ORIENT-16	Unresectable gastric or gastroesophageal Junction cancer	Sintilimab+XELOX vs Placebo+XELOX	Ⅲ	mOS: 18.4 months vs 12.9 months; mPFS: 7.7 months vs 5.8 months; ORR: 63.6% vs 49.4%
PD-L1 CPS≥1 vs PD-L1 CPS≥10	KEYNOTE-061	Previously treated, advanced gastric or gastro-oesophageal junction cancer	Pembrolizumab vs paclitaxel	Ⅲ	PD-L1 CPS≥1 mOS: 9.1 months vs 8.3 months, P=0.042 1*; mPFS: 1.5 months vs 4.1 months; ORR: 16% vs 14% PD-L1 CPS≥10 mOS: 10.4 months vs 8.0 months, P<0.000 1; ORR: 24.5% vs 9.1%
	KEYNOTE-859	Advanced or metastatic HER2- gastric or gastro-esophageal junction adenocarcinoma	Pembrolizumab+FP/XELOX vs placebo+P/XELOX	Ⅲ	PD-L1 CPS≥1 mOS: 13.0 months vs 11.4 months, P<0.000 1; ORR: 61% vs 43% PD-L1 CPS≥10 mOS: 15.7 months vs 11.8 months, P<0.000 1; ORR: 52% vs 43%
	KEYNOTE-062	Untreated, advanced gastric/gastroesophageal junction cancer	Pembrolizumab+ cisplatin/fluorouracil vs placebo+cisplatin/fluorouracil	Ⅲ	PD-L1 CPS≥1 mOS: 12.5 months vs 11.1 months, P=0.05*; ORR: 49% vs 37% PD-L1 CPS≥10 mOS: 12.3 months vs 10.8 months, P=0.16; ORR: 53% vs 37.8%
PD-L1 CPS≥5 vs PD-L1 CPS≥10	GEMSTONE-303	Untreated, advanced gastric/gastroesophageal junction cancer	Sugemalimab+XELOX vs Placebo+XELOX	Ⅲ	PD-L1 CPS≥5 mOS: 15.64 months vs 12.65 months; mPFS: 7.62 months vs 6.08 months PD-L1 CPS≥10 mOS: 17.81 months vs 12.45 months; mPFS: 7.79 months vs 5.52 months