中山大学肿瘤防治中心徐瑞华主任课题组比较了卡瑞利珠单抗与安慰剂联合化疗对晚期或转移性食管鳞癌患者生存期和无进展生存期的影响。这一研究成果发表在2021年9月14日出版的《美国医学会杂志》上。

晚期或转移性食管癌的标准一线治疗方法是化疗，但预后仍然很差。卡瑞利珠单抗是一种抗程序性死亡受体1（PD-1）抗体，此前在治疗晚期或转移性食管鳞癌中显示出抗肿瘤活性。

为了评估卡瑞利珠单抗联合化疗与安慰剂联合化疗作为晚期或转移性食管鳞癌一线治疗的疗效和不良事件，2018年12月3日至2020年5月12日，研究组在中国的60家医院进行了一项随机、双盲、安慰剂对照、多中心、临床3期试验，共招募了751名患者，并将596名未经治疗的晚期或转移性食管鳞癌患者按1：1随机分组，其中298例接受200 mg卡瑞利珠单抗治疗，298例接受安慰剂治疗，两组均联合使用多达6个周期的紫杉醇和顺铂化疗。所有治疗均每3周静脉注射一次。主要终点为总生存率和无进展生存率。

596名随机分组的患者中位年龄为62岁，523名为男性（87.8%），安慰剂-化疗组有1名患者未接受计划治疗。共有490名患者（82.2%）停止了研究治疗。中位随访时间为10.8个月。卡瑞利珠单抗-化疗组的中位总生存期为15.3个月，显著高于安慰剂-化疗组的12.0个月，死亡风险比为0.70。

卡瑞利珠单抗-化疗组的中位无进展生存期为6.9个月，显著高于安慰剂-化疗组的5.6个月，疾病进展或死亡的风险比为0.56。卡瑞利珠单抗-化疗组中有189名患者（63.4%）发生3级或更高级别的治疗相关不良事件，安慰剂-化疗组有201名患者（67.7%）；卡瑞利珠单抗-化疗组中有9名患者（3.0%）发生治疗相关死亡，安慰剂-化疗组中有11名患者（3.7%）死亡。

研究结果表明，对于晚期或转移性食管鳞癌患者，与安慰剂联合化疗相比，卡瑞利珠单抗联合化疗可显著提高患者的总生存期和无进展生存期。

附：英文原文

Title: Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial

Author: Huiyan Luo, Jin Lu, Yuxian Bai, Teng Mao, Jun Wang, Qingxia Fan, Yiping Zhang, Kuaile Zhao, Zhendong Chen, Shegan Gao, Jiancheng Li, Zhichao Fu, Kangsheng Gu, Zhihua Liu, Lin Wu, Xiaodong Zhang, Jifeng Feng, Zuoxing Niu, Yi Ba, Helong Zhang, Ying Liu, Li Zhang, Xuhong Min, Jing Huang, Ying Cheng, Dong Wang, Yu Shen, Qing Yang, Jianjun Zou, Rui-Hua Xu, ESCORT-st Investigators, Xianglin Yuan, Dong Ma, Li Liu, Feng Ye, Tianshu Liu, Xiuwen Wang, Likun Liu, Bing Xia, Fengming Ran, Sanyuan Sun, Zhanhui Miao, Jun Bie, Yong Gao, Junyan Yu, Li Chen, Yifu He, Wei Ren, Suxia Luo, Guangqiang Zhao, Youen Lin, Long Chen, Zhiyuan Guo, Chunhong Hu, Ying Wang, Nong Xu, Baofu Chen, Xianbao Zhan, Yuping Chen, Hongda Lu, Shukui Qin, Guolei Wang, Liming Chen, Li Bai, Jingdong Zhang

Issue&Volume: 2021/09/14

Abstract:

Importance  Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti–programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma.

Objective  To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma.

Design, Setting, and Participants  This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized.

Interventions  Patients were randomized 1:1 to receive either camrelizumab 200 mg (n=298) or placebo (n=298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks.

Main Outcomes and Measures  Coprimary end points were overall survival (significance threshold, 1-sided P<.02) and progression-free survival (significance threshold, 1-sided P<.005).

Results  Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P=.001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P<.001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively.

Conclusions and Relevance  Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival.

DOI: 10.1001/jama.2021.12836

Source: https://jamanetwork.com/journals/jama/article-abstract/2784143