抗EGFR单抗联合免疫检查点抑制剂治疗头颈部鳞状细胞癌专家共识（2025年版）

doi:10.19401/j.cnki.1007-3639.2025.05.010

摘要/Abstract

摘要：

头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）是头颈部肿瘤最为常见的一种类型，其治疗效果及患者的预后并不理想，随着抗表皮生长因子受体（epidermal growth factor receptor，EGFR）单抗和免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）的广泛应用，HNSCC患者的生存期虽有所延长但仍存在较大的改善空间。近年来多项研究提示，抗EGFR单抗联合ICIs治疗可带来良好的效果及安全性，已获得美国国立综合癌症网络（National Comprehensive Cancer Network，NCCN）和中国临床肿瘤学会（Chinese Society of Clinical Oncology，CSCO）等发布的权威性指南推荐。然而，抗EGFR单抗联合ICIs治疗方案的应用仍处于早期探索阶段，如何在临床中规范使用仍存在诸多待解答的问题，包括其协同作用机制、在不同类型患者中的治疗价值及安全性等。CSCO头颈肿瘤专家委员会组织专家基于循证医学证据及临床实践探索，经过多轮讨论，最终形成《抗EGFR单抗联合免疫检查点抑制剂治疗头颈部鳞状细胞癌专家共识（2025年版）》，对抗EGFR单抗与ICIs联合治疗的作用机制、分层治疗、在特殊人群中的应用及安全性等方面提出指导建议。本共识已在国际实践指南注册与透明化平台（Practice guideline REgistration for transPAREncy，PREPARE）上注册，注册号为PREPARE-2025CN666。期望本共识能够为临床医师提供更为明确和实用的指导，进一步推动该联合方案在临床实践中的合理应用，为HNSCC患者提供更多的治疗选择。

关键词: 头颈部鳞状细胞癌, 抗表皮生长因子受体单抗, 免疫检查点抑制剂, 联合治疗, 安全性, 专家共识

Abstract:

Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer, and its treatment prognosis remains suboptimal. Although the survival of HNSCC patients has improved with the widespread use of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and immune checkpoint inhibitors (ICIs), there is still significant room for further improvement. Recent studies have suggested that the combination of anti-EGFR monoclonal antibodies and ICIs offers promising efficacy and safety, earning recommendations from authoritative guidelines such as the National Comprehensive Cancer Network (NCCN) and the Chinese Society of Clinical Oncology (CSCO). However, the application of this combination therapy is still in the early exploratory stage, numerous questions regarding the standardized clinical use of this combination therapy remain unanswered, including the mechanisms of synergy associated with the combination treatment, its therapeutic value in different patient populations, and safety considerations. Committee of Head and Neck Cancer, Chinese Society of Clinical Oncology organized an expert panel to develop “Expert consensus on the combination of anti-EGFR monoclonal antibodies and immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma (2025 edition)”, based on evidence-based medicine and clinical practice exploration through multiple rounds of discussions. This consensus addressed the mechanisms of the combination of anti-EGFR monoclonal antibodies and ICIs, stratified treatment approaches, applications in special populations, and safety considerations. The consensus has been registered on Practice guideline REgistration for transPAREncy (PREPARE) with the registration number PREPARE-2025CN666. It is hoped that this consensus will provide clearer and more practical guidance for clinicians, further promoting the rational application of this combination therapy in clinical practice and offering more treatment options for HNSCC patients.

Key words: Head and neck squamous cell carcinoma, Anti-epidermal growth factor receptor monoclonal antibodies, Immune checkpoint inhibitors, Combination treatment, Safety, Expert consensus

中图分类号:

R739.91

薛丽琼, 许婷婷, 郭晔, 胡超苏. 抗EGFR单抗联合免疫检查点抑制剂治疗头颈部鳞状细胞癌专家共识（2025年版）[J]. 中国癌症杂志, 2025, 35(5): 510-522.

XUE Liqiong, XU Tingting, GUO Ye, HU Chaosu. Expert consensus on the combination of anti-EGFR monoclonal antibodies and immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma (2025 edition)[J]. China Oncology, 2025, 35(5): 510-522.

图/表 3

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编号	陈述	非常同意率	基本同意率	不确定或不同意率	同意率
1	临床前研究提示，抗EGFR单抗可能通过增强肿瘤抗原递呈和影响免疫微环境等机制，实现与ICIs的协同增效作用	74%（23/31)	26%（8/31）	0%（0/31）	100%（31/31)
2	对于不耐受或拒绝化疗的R/M HNSCC，可以考虑ICIs联合抗EGFR单抗作为一线治疗方案	81%（25/31)	19%（6/31)	0%（0/31）	100%（31/31)
3	抗EGFR单抗、ICIs和化疗的联合方案一线治疗R/M HNSCC初步显示出很高的ORR，但不良反应有所增加，可以考虑在高度选择的患者中使用	65%（20/31)	35%（11/31)	0%（0/31）	100%（31/31)
4	对于铂类药物耐药或治疗失败的R/M HNSCC，可以考虑抗EGFR单抗联合ICIs的治疗方案	74%（23/31)	26%（8/31)	0%（0/31）	100%（31/31)
5	对于一线接受ICIs治疗失败的R/M HNSCC，抗EGFR单抗单药或联合化疗是常用的挽救治疗方案，再次联合ICIs的获益尚不明确	65%（20/31)	32%（10/31)	3%（1/31）	97%（30/31)
6	抗EGFR单抗联合ICIs治疗方案的安全性良好，联合治疗并没有明显增加抗EGFR单抗或ICIs单药的毒性	65%（20/31)	35%（11/31)	0%（0/31）	100%（31/31)
7	对于不耐受顺铂的LA HNSCC，放疗联合抗EGFR单抗是常用的非手术治疗方案，初步证据显示在此基础上再联合ICIs有助于改善PFS和降低远处转移发生率	39%（12/31)	61%（19/31)	0%（0/31）	100%（31/31)
8	对于适合接受根治性手术的LA HNSCC，抗EGFR单抗联合ICIs和化疗的新辅助治疗方案初步显示出很高的病理学缓解率，具有潜在的器官功能保留价值和可接受的安全性	55%（17/31)	45%（14/31)	0%（0/31）	100%（31/31)

NCT	期别	治疗方案	治疗线数	样本量 n	铂类药物耐药 n (%)	ICIs暴露 n (%)	西妥昔单抗暴露 n (%)	ORR/%	中位PFS/月	中位OS/月
NCT03370276^[31]	Ⅱ期	西妥昔单抗+纳武利尤单抗	一线	43	-	-	-	37.2	6.15	20.2
NCT04856631^[32]	Ⅱ期	西妥昔单抗+特瑞普利单抗	一线	43	-	-	-	41.9	8.2	18.1
NCT05673577^[33]	Ⅱ期	西妥昔单抗+卡瑞利珠单抗+白蛋白结合型紫杉醇+顺铂	一线	21	-	-	-	90.5	NR	NR
NCT03082534^[34]	Ⅱ期	西妥昔单抗+帕博利珠单抗	一线+后线	33	17 (51.5)	0 (0.0)	0 (0.0)	45.0	6.5	18.4
NCT04856631^[35]	Ⅱ期	西妥昔单抗+特瑞普利单抗	后线	45	20 (44.4)	0 (0.0)	0 (0.0)	60.0	9.9	15.4
NCT03370276^[31,36]	Ⅱ期	西妥昔单抗+纳武利尤单抗	后线	45	10 (22.2)	22 (48.9)	NR	22.2	3.4	11.4
NCT03691714^[37]	Ⅱ期	西妥昔单抗+度伐利尤单抗	一线+后线	33	NR	10 (30.3)	1 (3.0)	39.0	5.8	9.6

治疗线数	治疗方案	样本量 n	3级及以上TRAE n (%)	常见的3级及以上TRAE（≥5%）
一线	帕博利珠单抗+化疗^[8]	276	198 (71.7)	贫血：54 (20%)；中性粒细胞减少：49 (18%)；血小板减少：24 (9%)；黏膜炎：26 (9%)；口腔炎：22 (8%)；疲劳：19 (7%)；恶心：15 (5%)
一线	帕博利珠单抗^[8]	300	51 (17.0)	-
一线	西妥昔单抗+纳武利尤单抗^[31]	43	10 (23.3)	痤疮样皮疹：4 (9%)；低镁血症：2 (5%)；低磷血症：2 (5%)
一线	西妥昔单抗+特瑞普利单抗^[32]	43	13 (30.2)	NR^a
一线+后线	西妥昔单抗+帕博利珠单抗^[34]	33	14 (42.4)	口腔黏膜炎：3 (9%)；结肠炎：2 (6%)；痤疮样皮疹：2 (6%)；低镁血症：2 (6%)
一线+后线	西妥昔单抗+度伐利尤单抗^[37]	33	17 (51.5)	-
后线	西妥昔单抗^[12]	103	21 (20.4)	-
后线	纳武利尤单抗^[10]	236	31 (13.1)	-
后线	帕博利珠单抗^[11]	246	33 (13.4)	-
后线	西妥昔单抗+特瑞普利单抗^[35]	45	10 (22.2)	NR^b
后线	西妥昔单抗+纳武利尤单抗^[36]	45	14 (31.1)	疲劳：6 (13%)