帕博利珠单抗联合白蛋白结合型紫杉醇和铂类一线治疗复发转移性头颈部鳞癌:一项前瞻性Ⅱ期临床研究  

Pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma:a prospective phaseⅡstudy

作　　者：陈馨蕊 谢祖成 鲁海珍 杨建良 桂琳 Chen Xinrui;Xie Zucheng;Lu Haizhen;Yang Jianliang;Gui Lin(Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs,Beijing 100021,China;Department of Pathology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100021,China)

机构地区：[1]国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院北京协和医学院肿瘤医院内科、抗肿瘤分子靶向药物临床研究北京市重点实验室,北京100021 [2]国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院北京协和医学院肿瘤医院病理科,北京100021

出　　处：《中华耳鼻咽喉头颈外科杂志》2024年第4期321-328,共8页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：中国癌症基金会北京希望马拉松专项基金(LC2022A30);中国医学科学院肿瘤医院内科重点学科基金重点基金(CICAMS-MOMP2022010)。

摘　　要：目的评价帕博利珠单抗联合白蛋白结合型紫杉醇和铂类一线治疗复发/转移性头颈部鳞状细胞癌(recurrent or metastatic head and neck squamous-cell carcinoma,R/M HNSCC)患者的疗效和安全性。方法本研究为前瞻性、单臂、开放、Ⅱ期临床研究,纳入中国医学科学院肿瘤医院即将接受晚期一线治疗的R/M HNSCC患者,进行帕博利珠单抗联合白蛋白结合型紫杉醇和顺铂或卡铂方案治疗;治疗6周期,疾病获得控制的患者继续帕博利珠单抗维持治疗至疾病进展或出现不可耐受的毒性或完成共35周期的治疗。主要研究终点为客观缓解率,次要研究终点包括总生存期、无进展生存期和安全性指标。按实体瘤疗效评价标准1.1版进行疗效评价,生存分析采用Kaplan-Meier法,不良事件采用美国国家癌症研究所不良事件通用术语标准5.0版进行评估。结果2021年4月23日至2023年3月22日共纳入30例R/M HNSCC患者,其中男性28例,女性2例,中位年龄为67岁。中位随访时间为14.5个月,客观缓解率为70.0%,疾病控制率为96.7%,中位无进展生存期和总生存期分别为11.6个月和18.8个月,中位缓解持续时间为17.3个月。≥3级的治疗相关不良事件包括白细胞减少(26.7%)、中性粒细胞减少(26.7%)、外周神经毒性(3.3%)、皮疹(3.3%)、肾上腺皮质功能减退(3.3%)和免疫相关性肺炎(3.3%);最常见的免疫相关不良事件是甲状腺功能减退(40.0%)。结论帕博利珠单抗联合白蛋白结合型紫杉醇和铂类方案一线治疗中国R/M HNSCC患者初步显示出较好的抗肿瘤活性和良好的耐受性。Objective To evaluate the efficacy and safety of pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma(R/M HNSCC).Methods This was a prospective,single-arm,open label,phase 2 clinical study enrolling patients at the Cancer Hospital of the Chinese Academy of Medical Sciences with R/M HNSCC treated with pembrolizumab plus nab-paclitaxel and cisplatin or carboplatin.After six cycles of treatment,patients received pembrolizumab as maintenance therapy until disease progression or intolerable toxicity or completion of 35 cycles of treatment.The primary endpoint was objective response rate,and secondary endpoints included overall survival,progression-free survival,and safety profile.Efficacy was evaluated according to the response evaluation criteria in solid tumors 1.1,survival analysis was performed using the Kaplan-Meier method,and adverse events were assessed using the America National Cancer Institute Common Terminology Criteria for Adverse Events 5.0.Results A total of 30 patients with R/M HNSCC were enrolled from 23 April 2021 to 22 March 2023,including 28 males and 2 females,with a median age of 67 years.The median follow-up time was 14.5 months,the objective response rate was 70.0%,the disease control rate was 96.7%,and the median progression-free survival and overall survival of all patients were 11.6 months and 18.8 months,respectively.Median duration of response was up to 17.3 months.Grade≥3 treatment-related adverse events were leukopenia(26.7%),neutropenia(26.7%),peripheral neurotoxicity(3.3%),rash(3.3%),hyperalgesia(3.3%),and immune-related pneumonitis(3.3%).The most common immune-related adverse event was hypothyroidism(40.0%).Conclusion Pembrolizumab combined with nab-paclitaxel and platinum shows encouraging antitumor activity accompanied with a manageable safety profile in untreated R/M HNSCC patients in China.

关 键 词：头颈部肿瘤 癌 鳞状细胞 帕博利珠单抗 白蛋白结合型紫杉醇 铂类 

分 类 号：R739.91[医药卫生—肿瘤]