Journal Article

Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial

Li, Hecheng, Yang, Zhaoyang, Li, Lin, Han, Yongtao, Hou, Zhiguo, Wang, Zhen, Yang, Hao, Li, Yong, Guo, Xiaofeng, Kang, Xiaozheng, Liu, Shuoyan, Zhang, Weiguo, Li, Yin, Li, Chengqiang, Chen, Yujie, Chen, Longqi, Dai, Tianyang, Hao, Anlin, Zhang, Ruixiang, Jiang, Tao, Fu, Maoyong, Tian, Hui, Liao, Yongde, Ma, Jianqun, Tian, Ziqiang, Ni, Yunfeng, He, Jie, Lin, Jihong, Tan, Lijie, Wang, Xiaoyuan, Zhu, Wenqing, Xue, Liyan, Zhang, Chen, Fu, Junke, Jiang, Hongjing, Zheng, Rongrong, Li, Zhigang, Chen, Xiankai, Chen, Qixun, Qin, Jianjun, Li, Bin, Kang, Mingqiang, Guo, Shiping, Qi, Yu, Zhang, Yong, Wei, Li

2024

Overview

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n  = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n  = 130); and paclitaxel with cisplatin (TP group; n  = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1–32.0, P  < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7–18.1, P  = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 . In a randomized phase 3 trial, neoadjuvant anti-PD-1 plus either paclitaxel and cisplatin or nab-paclitaxel and cisplatin elicited a significantly superior pathological complete response rate versus neoadjuvant paclitaxel and cisplatin alone in patients with resectable locally advanced esophageal squamous cell carcinoma.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/308/2779/777 / 692/699/67/1059/2325 / 692/699/67/1059/99 / 692/699/67/1504/1477 / Adult / Aged / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - therapeutic use / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Biomedical and Life Sciences / Biomedicine / Cancer Research / Chemotherapy / Cisplatin / Cisplatin - administration & dosage / Cisplatin - therapeutic use / Complications / Cycle ratio / Esophageal cancer / Esophageal carcinoma / Esophageal Neoplasms - drug therapy / Esophageal Neoplasms - pathology / Esophageal Squamous Cell Carcinoma - drug therapy / Esophageal Squamous Cell Carcinoma - pathology / Esophageal Squamous Cell Carcinoma - surgery / Esophagus / Female / Humans / Infectious Diseases / Male / Metabolic Diseases / Middle Aged / Molecular Medicine / Neoadjuvant Therapy / Neurosciences / Paclitaxel / Paclitaxel - administration & dosage / Paclitaxel - adverse effects / Paclitaxel - therapeutic use / Patients / PD-1 protein / Population studies / Postoperative / Squamous cell carcinoma / Thorax