中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (12): 1220-1232.

• 指南与共识 • 上一篇    

抗EGFR单抗治疗复发/转移性头颈部鳞状细胞癌临床共识(2021年版)

郭 晔 1 ,张陈平 2   

  1. 1. 中国临床肿瘤学会头颈肿瘤专家委员会,上海 200123 ;
    2. 上海市抗癌协会头颈肿瘤专业委员会,上海 200032
  • 出版日期:2021-12-30 发布日期:2021-12-29
  • 通信作者: 郭 晔 E-mail: pattrickguo@gmail.com;张陈平 E-mail: zhang.chenping@hotmail.com

Expert consensus on the treatment of recurrent/metastatic squamous cell carcinoma of the head and neck with anti-EGFR monoclonal antibody (2021 edition)

GUO Ye 1 , ZHANG Chenping   

  1. 1. Head and Neck Tumor Committee of Chinese Society of Clinical Oncology, Shanghai 200123, China; 2. Head and Neck Tumor Committee of Shanghai Anticancer Association, Shanghai 200032, China
  • Published:2021-12-30 Online:2021-12-29
  • Contact: GUO Ye E-mail: pattrickguo@gmail.com; ZHANG Chenping E-mail: zhang.chenping@hotmail.com

摘要: 头颈部鳞状细胞癌(squamous cell carcinoma of the head and neck,SCCHN)是头颈部肿瘤最为常见的一种类型,其疾病负担较重。SCCHN患者中,90%以上高表达表皮生长因子受体(epidermal growth factor receptor,EGFR),因此通过单克隆抗体特异性地与EGFR结合,是抑制EGFR信号转导的一种重要方法。目前多种基于EGFR受体及其通路相关的靶向药物中,西妥昔单抗是唯一疗效确切的药物,已于2020年2月在中国获批用于一线治疗复发/转移性SCCHN(recurrent/metastatic SCCHN,R/M SCCHN),随着西妥昔单抗逐步应用于临床,中国晚期SCCHN患者整体的治疗模式将不断得到优化和提升。值得注意的是,虽然靶向和免疫药物在SCCHN的治疗中取得了很大的进展,但仍然存在很多挑战,其中西妥昔单抗治疗R/M SCCHN在EGFR检测、药物应用时机、联合方案和应用剂量以及不良反应管理等方面尚未达成共识。本共识就西妥昔单抗用于R/M SCCHN一线、二线以及联合免疫治疗时的疗效和安全性,结合文献及中国临床实践进行阐述,并对相关治疗方案予以推荐,希望对西妥昔单抗规范化治疗SCCHN患者及优化临床实践提供指导。经过多轮商议和探讨,共识小组的专家汇总出以下推荐意见。在分子检测方面,R/M SCCHN患者无需常规检测EGFR以指导临床实践,抗EGFR单克隆抗体通过抑制EGFR信号转导起到抗肿瘤作用。一线治疗中,对于铂类药物耐受患者,建议6个周期的西妥昔单抗联合顺铂75 mg/m 2 ,5-FU 750 mg/m 2 治疗,疾病缓解或稳定后继续接受西妥昔单抗单药维持治疗至疾病进展;对于有5-FU治疗禁忌证、持续静脉输液不方便、二氢嘧啶脱氢酶(dihydropyrimidine dehydrogenase,DPD)缺乏症及治疗依从性差的患者,建议4个周期的西妥昔单抗联合铂类药物(顺铂75 mg/m 2 ,每3周1次)+多西他赛(75 mg/m 2 ,每3周1次)治疗,疾病缓解或稳定后继续接受西妥昔单抗单药维持治疗至疾病进展;对于铂类药物不耐受的患者,建议西妥昔单抗联合紫杉醇每周方案治疗,直至疾病进展;对于身体状况良好的老年患者,建议西妥昔单抗+卡铂+5-FU治疗6个周期后,使用西妥昔单抗维持治疗。多个临床研究和真实世界数据均显示,西妥昔单抗联合化疗一线治疗显示出一致的高客观缓解率(objective response rate,ORR)和生存获益。二线治疗中,对于一线含铂类药物化疗方案治疗失败的患者,建议西妥昔单抗单药治疗或联合紫杉醇每周方案治疗;对于一线免疫检查点抑制剂(immune checkpoint inhibitor,ICI)治疗失败的患者,建议西妥昔单抗联合化疗方案,其中联合药物应基于之前的药物暴露加以调整。安全性方面,西妥昔单抗治疗方案相关的常见不良事件包括皮肤反应、输液反应和电解质紊乱。多数皮肤反应是轻度的,可以通过预防措施加以控制,在西妥昔单抗停药或减少剂量后,这些不良反应通常会消失而无后遗症。输液反应可通过输注前预防、输注时及输注后密切监测和及时干预加以有效控制。与单纯化疗相比,西妥昔单抗治疗相关的不良反应通常耐受性良好并且可接受。此外,西妥昔单抗联合免疫治疗或新型靶向药物的应用正在探索中,未来将为R/M SCCHN患者带来更多选择。

关键词: 表皮生长因子受体, 抗表皮生长因子受体抗体, 复发/转移性头颈部鳞状细胞癌, 共识, 靶向治疗

Abstract: Squamous cell carcinoma of the head and neck (SCCHN) is the most common head and neck tumor, with higher disease burden. More than 90% SCCHN patients with overexpression of epidermal growth factor receptor (EGFR). Therefore, one important method to inhibit EGFR signaling is through the specific high affinity binding of monoclonal antibody to EGFR. Among a variety of current drugs targeting EGFR and its pathway, cetuximab is the only targeted drug with definite efficacy and has been approved in China since February 2020 for the first-line treatment of recurrent/metastatic SCCHN (R/M SCCHN). With the gradual clinical application of cetuximab, the overall treatment model for patients with advanced SCCHN in China will continue to be improved and optimized. It is worth noting that although targeted and immune drugs have made great progress in the treatment of SCCHN, there are still many challenges. Consensus has not yet been reached for cetuximab on EGFR detection, drug application timing, combination regimen and suitable dosage, and adverse reaction management in the treatment of R/M SCCHN. This expert consensus has combined the literature and clinical practice in China to explain the efficacy and safety of cetuximab in first-line, second-line and combined immunotherapy of R/M SCCHN, and provides relevant recommendations regarding treatment strategies. It is hoped that this consensus will provide guidance for the standardized treatment of SCCHN patients with cetuximab and the optimization of clinical practice. After several rounds of discussion, experts of the consensus group have provided the following recommendations. In terms of molecular testing, patients with R/M SCCHN do not need routine testing of EGFR to inform clinical practice. Anti-EGFR monoclonal antibodies exert anti-tumor effect by inhibiting EGFR signaling. In first-line treatment, 6 cycles of cetuximab in combination with cisplatin 75 mg/m 2 and 5-FU 750 mg/m 2 are recommended for platinum-tolerant patients, followed with cetuximab maintenance monotherapy after disease response or stable disease until progressive disease; 4 cycles of cetuximab in combination with platinum (cisplatin 75 mg/m 2 , q3w) + docetaxel (75 mg/m 2 , q3w) are recommended for patients with contraindications to 5-FU, inconvenience with continuous intravenous infusion, dihydropyrimidine dehydrogenase (DPD) deficiency and poor treatment compliance, followed with cetuximab maintenance monotherapy after disease response or stable disease until progressive disease; cetuximab in combination with paclitaxel weekly is recommended for platinum-intolerant patients until progressive disease; and cetuximab maintenance monotherapy is recommended for elderly patients in good condition after 6 cycles of cetuximab + carboplatin + 5-FU. Multiple clinical studies and real-world data have shown consistent high objective response rate (ORR) and survival benefit with cetuximab in combination with chemotherapy in first-line treatment. In second-line treatment, for patients who have failed first-line platinum-based chemotherapy, weekly treatment with cetuximab monotherapy or in combination with paclitaxel is recommended; for patients who have failed first-line immune checkpoint inhibitor (ICI) treatment, cetuximab in combination with chemotherapy is recommended, and the combined drugs should be adjusted based on previous drug exposure. In terms of safety, the most common adverse events related to cetuximab treatment include skin reaction, infusion reaction and electrolyte disturbance. Most skin reactions are mild and manageable with precautions and generally will resolve without sequelae upon discontinuation or dose reduction of cetuximab. Infusion reactions can be effectively controlled by precautions before infusion, close monitoring during and after infusion and timely intervention. Adverse reactions associated with cetuximab treatment are generally well tolerated and acceptable compared with those associated with chemotherapy alone. In addition, the use of cetuximab in combination with immunotherapy or new targeted drugs is explored and will bring more possibilities for R/M SCCHN patients in the future.

Key words: Epidermal growth factor receptor, Anti-epidermal growth factor receptor antibody, Recurrent/metastatic squamous cell carcinoma of the head and neck, Consensus, Targeted therapy