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)

Liqiong XUE; Tingting XU; Ye GUO; Chaosu HU

doi:10.19401/j.cnki.1007-3639.2025.05.010

您当前的位置：

首页 >

文章列表页 >

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)

Original article | 更新时间：2025-12-31

- 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)
- China Oncology Vol. 35, Issue 5, Pages: 510-522(2025)
- 作者机构：
  
  中国临床肿瘤学会头颈肿瘤专家委员会
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2025.05.010
  CLC： R739.91
- Received：16 April 2025，
  
  Revised：2025-05-16，
  
  Published：30 May 2025
- 稿件说明：
移动端阅览
Liqiong XUE, Tingting XU, Ye GUO, et al. 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.
DOI：

Liqiong XUE, Tingting XU, Ye GUO, et al. 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. DOI： 10.19401/j.cnki.1007-3639.2025.05.010.

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。

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.

关键词

Keywords

references

HAN B F , ZHENG R S , ZENG H M , et al. Cancer incidence and mortality in China, 2022 [J ] . J Natl Cancer Cent , 2024 , 4 ( 1 ): 47 - 53 .

MODY M D , ROCCO J W , YOM S S , et al. Head and neck cancer [J ] . Lancet , 2021 , 398 ( 10318 ): 2289 - 2299 . DOI: 10.1016/S0140-6736(21)01550-6 http://doi.org/10.1016/S0140-6736(21)01550-6

SHAIKH H , KARIVEDU V , WISE-DRAPER T M . Managing recurrent metastatic head and neck cancer [J ] . Hematol Oncol Clin North Am , 2021 , 35 ( 5 ): 1009 - 1020 .

VERMORKEN J B , MESIA R , RIVERA F , et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer [J ] . N Engl J Med , 2008 , 359 ( 11 ): 1116 - 1127 .

MESÍA R , RIVERA F , KAWECKI A , et al. Quality of life of patients receiving platinum-based chemotherapy plus cetuximab first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck [J ] . Ann Oncol , 2010 , 21 ( 10 ): 1967 - 1973 . DOI: S0923-7534(19)39580-8 http://doi.org/S0923-7534(19)39580-8

GUO Y , LUO Y , ZHANG Q Y , et al. First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: efficacy and safety results of the randomised, phase Ⅲ CHANGE-2 trial [J ] . Eur J Cancer , 2021 , 156 : 35 - 45 .

GUIGAY J , AUPÉRIN A , FAYETTE J , et al. Cetuximab, docetaxel, and cisplatin versus platinum, fluorouracil, and cetuximab as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (GORTEC 2014-01 TPExtreme): a multicentre, open-label, randomised, phase 2 trial [J ] . Lancet Oncol , 2021, 22 ( 4 ): 463 - 475 .

BURTNESS B , HARRINGTON K J , GREIL R , et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study [J ] . Lancet , 2019 , 394 ( 10212 ): 1915 - 1928 . DOI: S0140-6736(19)32591-7 http://doi.org/S0140-6736(19)32591-7

BURTNESS B , RISCHIN D , GREIL R , et al. Pembrolizumab alone or with chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048: subgroup analysis by programmed death ligand-1 combined positive score [J ] . J Clin Oncol , 2022 , 40 ( 21 ): 2321 - 2332 .

FERRIS R L , BLUMENSCHEIN G Jr , FAYETTE J , et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck [J ] . N Engl J Med , 2016 , 375 ( 19 ): 1856 - 1867 .

COHEN E E W , SOULIÈRES D , LE TOURNEAU C , et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study [J ] . Lancet , 2019 , 393 ( 10167 ): 156 - 167 . DOI: S0140-6736(18)31999-8 http://doi.org/S0140-6736(18)31999-8

VERMORKEN J B , TRIGO J , HITT R , et al. Open-label, uncontrolled, multicenter phase Ⅱ study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy [J ] . J Clin Oncol , 2007 , 25 ( 16 ): 2171 - 2177 .

FUEREDER T , KLINGHAMMER K , HAHN D A , et al. Paclitaxel plus cetuximab for the treatment of recurrent and/or metastatic head and neck cancer after first-line checkpoint inhibitor failure: primary analysis from the pace ace trial [J ] . Ann Oncol , 2024 , 35 : S629 .

KOYAMA T , KIYOTA N , BOKU S , et al. A phase Ⅱ trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody [J ] . ESMO Open , 2024 , 9 ( 6 ): 103476.

GILLISON M L , BLUMENSCHEIN G Jr , FAYETTE J , et al. CheckMate 141: 1-year update and subgroup analysis of nivolumab as first-line therapy in patients with recurrent/metastatic head and neck cancer [J ] . Oncologist , 2018 , 23 ( 9 ): 1079 - 1082 . DOI: 10.1634/theoncologist.2017-0674 http://doi.org/10.1634/theoncologist.2017-0674

POINTREAU Y , GARAUD P , CHAPET S , et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation [J ] . J Natl Cancer Inst , 2009 , 101 ( 7 ): 498 - 506 . DOI: 10.1093/jnci/djp007 http://doi.org/10.1093/jnci/djp007

KEIL F , HARTL M , ALTORJAI G , et al. Docetaxel, cisplatin and 5-FU compared with docetaxel, cisplatin and cetuximab as induction chemotherapy in advanced squamous cell carcinoma of the head and neck: results of a randomised phase Ⅱ AGMT trial [J ] . Eur J Cancer , 2021 , 151 : 201 - 210 .

KÜRTEN C H L , FERRIS R L . Neoadjuvant immunotherapy for head and neck squamous cell carcinoma [J ] . Laryngorhinootologie , 2024 , 103 ( s 01 ): S167 -S187. DOI: 10.1055/a-2183-5802 http://doi.org/10.1055/a-2183-5802

Merck’s KEYTRUDA ® (pembrolizumab) Met primary endpoint of event-free survival (EFS) as perioperative treatment regimen in patients w ith resected, locally advanced head and neck squamous cell carcinoma [EB/OL ] . [ 2025-04-15 ] . https://www.merck.com/news/mercks-keytruda-pembrolizumab-met-primary-endpoint-of-event-free-survival-efs-as-perioperative-treatment-regimen-in-patients-with-resected-locally-advanced-head-and-neck-squamous-c/ https://www.merck.com/news/mercks-keytruda-pembrolizumab-met-primary-endpoint-of-event-free-survival-efs-as-perioperative-treatment-regimen-in-patients-with-resected-locally-advanced-head-and-neck-squamous-c/ https://www.merck.com/news/mercks-keytruda-pembrolizumab-met-primary-endpoint-of-event-free-survival-efs-as-perioperative-treatment-regimen-in-patients-with-resected-locally-advanced-head-and-neck-squamous-c/.

LEE N Y , FERRIS R L , PSYRRI A , et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial [J ] . Lancet Oncol , 2021 , 22 ( 4 ): 450 - 462 . DOI: 10.1016/S1470-2045(20)30737-3 http://doi.org/10.1016/S1470-2045(20)30737-3

MACHIELS J P , TAO Y G , LICITRA L , et al. Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial [J ] . Lancet Oncol , 2024 , 25 ( 5 ): 572 - 587 .

MELL L K , TORRES-SAAVEDRA P A , WONG S J , et al. Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial [J ] . Lancet Oncol , 2024 , 25 ( 12 ): 1576 - 1588 . DOI: 10.1016/S1470-2045(24)00507-2 http://doi.org/10.1016/S1470-2045(24)00507-2

TAO Y , AUPERIN A , SUN X , et al. Avelumab-cetuximab-radiotherapy versus standards of care (SoC) in patients (pts) with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): safety phase of randomized trial GORTEC 2017-01 (REACH) [J ] . Ann Oncol , 2019 , 30 : v454 .

National Comprehensive Cancer Network . NCCN clinical practice guidelines in oncology (NCCN guidelines) for head and neck cancers. Version 2.2025 [EB/OL ] . [ 2025-04-15 ] . https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf.

中国临床肿瘤学会指南工作委员会 . 中国临床肿瘤学会(CSCO)头颈部肿瘤诊疗指南-2024 [M ] . 北京 : 人民卫生出版社 , 2024 .

Guidelines Working Committee , Chinese Society of Clinical Oncology . Guidelines and Chinese Society of Clinical Oncology (CSCO):head and neck cancer (2024) [M ] . Beijing : People’s Medical Publishing House , 2024 .

中国抗癌协会肿瘤整体评估专业委员会 , 福建省抗癌协会癌痛专业委员会 . 奥沙利铂超敏反应全程管理中国专家共识(2024年版) [J ] . 中国癌症杂志 , 2024 , 34 ( 8 ): 785 - 805 . DOI: 10.19401/j.cnki.1007-3639.2024.08.008 http://doi.org/10.19401/j.cnki.1007-3639.2024.08.008

Cancer Assessment Society of China Anti-Cancer Association, Cancer Pain Society of Fujian Anti-Cancer Association . Chinese expert consensus on whole-process management of oxaliplatin-induced hypersensitivity reactions (2024 edition) [J ] . China Oncol , 2024 , 34 ( 8 ): 785 - 805 .

FERRIS R L , LENZ H J , TROTTA A M , et al. Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation [J ] . Cancer Treat Rev , 2018 , 63 : 48 - 60 . DOI: S0305-7372(17)30200-1 http://doi.org/S0305-7372(17)30200-1

SABA N F , CHEN Z G , HAIGENTZ M , et al. Targeting the EGFR and immune pathways in squamous cell carcinoma of the head and neck (SCCHN): forging a new alliance [J ] . Mol Cancer Ther , 2019 , 18 ( 11 ): 1909 - 1915 . DOI: 10.1158/1535-7163.MCT-19-0214 http://doi.org/10.1158/1535-7163.MCT-19-0214

KUMAGAI S , KOYAMA S , NISHIKAWA H . Antitumour immunity regulated by aberrant ERBB family signalling [J ] . Nat Rev Cancer , 2021 , 21 ( 3 ): 181 - 197 . DOI: 10.1038/s41568-020-00322-0 http://doi.org/10.1038/s41568-020-00322-0

TIAN X , ZHANG H Y , HAN Y M , et al. Current status and future prospects of combined immunotherapy and epidermal growth factor receptor inhibitors in head and neck squamous cell carcinoma [J ] . Cancer Treat Rev , 2025 , 132 : 102864 .

CHUNG C H , LI J N , STEUER C E , et al. Phase Ⅱ multi-institutional clinical trial result of concurrent cetuximab and nivolumab in recurrent and/or metastatic head and neck squamous cell carcinoma [J ] . Clin Cancer Res , 2022 , 28 ( 11 ): 2329 - 2338 .

GUO Y , LI D Z , LIN J , et al. 872P Safety and efficacy of toripalimab combined with cetuximab in PD-L1 positive untreated recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): a phase Ⅰb/Ⅱ study [J ] . Ann Oncol , 2024 , 35 : S625 .

JI D , SANG Y , LIU X , et al. A phase Ⅱ clinical trial of camrelizumab combined with cetuximab and chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) [J ] . Ann Oncol , 2024 , 35 : S626 .

SACCO A G , CHEN R F , WORDEN F P , et al. Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial [J ] . Lancet Oncol , 2021 , 22 ( 6 ): 883 - 892 . DOI: 10.1016/S1470-2045(21)00136-4 http://doi.org/10.1016/S1470-2045(21)00136-4

GUO Y , LI Z D , HU D S , et al. Updated safety and efficacy of toripalimab combined with cetuximab in platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC): a phase Ⅰb/Ⅱ clinical trial [J ] . J Immunother Cancer , 2023 , 11 ( Suppl 1 ): A769 .

CHUNG C H , BONOMI M , STEUER C E , et al. Concurrent cetuximab and nivolumab as a second-line or beyond treatment of patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results of phase Ⅰ/Ⅱ study [J ] . Cancers (Basel) , 2021 , 13 ( 5 ): 1180.

GULATI S , CRIST M , RIAZ M K , et al. Durvalumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, nonrandomized, phase Ⅱ clinical trial [J ] . Clin Cancer Res , 2023 , 29 ( 10 ): 1906 - 1915 .

HARRINGTON K J , BURTNESS B , GREIL R , et al. Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: updated results of the phase Ⅲ KEYNOTE-048 study [J ] . J Clin Oncol , 2023 , 41 ( 4 ): 790 - 802 .

BONNER J A , HARARI P M , GIRALT J , et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck [J ] . N Engl J Med , 2006 , 354 ( 6 ): 567 - 578 .

BONNER J A , HARARI P M , GIRALT J , et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival [J ] . Lancet Oncol , 2010 , 11 ( 1 ): 21 - 28 . DOI: 10.1016/S1470-2045(09)70311-0 http://doi.org/10.1016/S1470-2045(09)70311-0

TAO Y , AUPERIN A , SUN X , et al. Avelumab-cetuximab-radiotherapy (RT) versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): final analysis of randomized phase Ⅲ GORTEC 2017-01 REACH trial [J ] . Ann Oncol , 2024 , 35 : S616 .

DUNN L , CRACCHIOLO J , HO A L , et al. 859P Neoadjuvant cemiplimab with platinum-doublet chemotherapy and cetuximab to de-escalate surgery and omit adjuvant radiation in locoregionally advanced head & neck squamous cell carcinoma (HNSCC) [J ] . Ann Oncol , 2024 , 35 : S619 .

YAO Z W , WANG J S , JIANG Y Q , et al. Pembrolizumab plus cetuximab with neoadjuvant chemotherapy for head and neck squamous cell carcinoma [J ] . Head Neck , 2025 , 47 ( 1 ): 289 - 299 .

XUE L , HAN Y , ZHANG Q , et al. Efficacy and safety of a novel anti-EGFR ADC MRG003 in recurrent or metastatic squamous cell carcinoma of the head and neck patients [J ] . Ann Oncol , 2023 , 34 : S590 .

HANNA G J , KACZMAR J , ZANDBERG D P , et al. Updated dose expansion results of a phase 1/1b study of the bifunctional EGFR/TGFβ inhibitor BCA101 with pembrolizumab in patients with recurrent, metastatic head and neck squamous cell carcinoma [J ] . Int J Radiat Oncol , 2024 , 118 ( 5 ): e88.

Views

1956

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

MDT consensus on immunotherapy for locally advanced head and neck squamous cell carcinoma (2025 edition)

Expert consensus on diagnosis and treatment of hematologic malignancies with solid tumors (2025 version)

Survival impact of corticosteroid and immunosuppressant management strategies for immune-related adverse events in immune checkpoint inhibitor-treated patients: a systematic review and meta-analysis

Research progress on treatment of pleural effusion related to immune checkpoint inhibitors

Chinese expert consensus on perioperative integrated rehabilitation for radical prostatectomy (2024 edition)

Related Author

Ye GUO

Chaosu HU

Chenping ZHANG

Multiple Primary and Unknown Primary Tumors Special Committee of China Anti-Cancer Association

Shanghai Anti Cancer Association Multiple Primary and Unknown Primary Tumor Special Committee

Lymphocytic Disease Group, Hematology Branch, Chinese Medical Association

Rare Disease Group, Hematology Branch, Chinese Medical Association

Xinyue LAN

Related Institution

Department of Medical Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine

Clinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine

Department of Oncology, The First Affiliated Hospital of Zhengzhou University

Department of Medical Oncology, Affiliated Hospital of Chuanbei Medical College, Nanchong

Head and Neck Cancer Committee of Chinese Anti-Cancer Association

AI问答

⁰