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)

doi:10.19401/j.cnki.1007-3639.2025.05.010

Abstract

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

CLC Number:

R739.91

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.

Figures/Tables 3

References 45

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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%)