Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002)

Xiaobin Shang, Wencheng Zhang, Gang Zhao, Fei Liang, Chen Zhang, Jie Yue, Xiaofeng Duan, Zhao Ma, Chuangui Chen, Qingsong Pang, Weihong Zhang, Liang Liu, Xiubao Ren, Bin Meng, Peng Zhang, Yegang Ma, Lin Zhang, Hecheng Li, Xiaozheng Kang, Yin Li, Hongjing Jiang, Xiaobin Shang, Wencheng Zhang, Gang Zhao, Fei Liang, Chen Zhang, Jie Yue, Xiaofeng Duan, Zhao Ma, Chuangui Chen, Qingsong Pang, Weihong Zhang, Liang Liu, Xiubao Ren, Bin Meng, Peng Zhang, Yegang Ma, Lin Zhang, Hecheng Li, Xiaozheng Kang, Yin Li, Hongjing Jiang

Abstract

Background: To compare the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy (neoCT) versus neoadjuvant chemoradiotherapy (neoCRT) followed by surgery for locally advanced resectable oesophageal squamous cell carcinoma (ESCC).

Methods: This study is a multicentre, prospective, randomized-controlled, phase III clinical study. Eligible ESCC (staging: cT1N2M0 or cT2-3N0-2M0 (stage II/III, high-risk lesions in T2N0M0)) patients will be randomly assigned to either the experimental group (pembrolizumab with neoCT, n = 228) or the control group (neoCRT, n = 114) at a ratio of 2:1. Within 4-6 weeks after preoperative therapy, the McKeown procedure will be performed. Patients in the experimental group will also receive pembrolizumab alone as adjuvant therapy after surgery until 1 year or until the radiographically confirmed PD or other condition indicated for premature termination is observed. The primary endpoint is event-free survival (EFS). The secondary endpoints are 1-, 3-, and 5-year overall survival (OS) and disease-free survival (DFS), short-term outcomes, and quality of life.

Discussion: This is the first prospectively randomized controlled trial designed to compare pembrolizumab plus chemotherapy and chemoradiotherapy as neoadjuvant therapy for resectable ESCC. According to our hypothesis, preoperative pembrolizumab combined with chemotherapy will result in a better tumour response and prolong the survival of patients, with acceptable toxicity. This study started in December 2021, and the enrolment time is estimated to be 2 years.

Trial registration: This prospective study has been registered at ClinicalTrials.gov (NCT04807673), March 2021.

Keywords: efficacy; event-free survival (EFS); immunotherapy; neoadjuvant therapy; oesophageal cancer (EC).

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Shang, Zhang, Zhao, Liang, Zhang, Yue, Duan, Ma, Chen, Pang, Zhang, Liu, Ren, Meng, Zhang, Ma, Zhang, Li, Kang, Li and Jiang.

Figures

Figure 1
Figure 1
Study flowchart. *Considering the long enrolment time, the postoperative treatment in the neoCRT group might be adjusted according to the updated guidelines.
Figure 2
Figure 2
The therapeutic strategy for enrolled patients. Pem, pembrolizumab; P, paclitaxel; C, cisplatin. *Considering the long enrolment time, the postoperative treatment in the neoCRT group might be adjusted according to the updated guidelines.

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Source: PubMed

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