Adjuvant immunotherapy for esophageal squamous cell carcinoma after neoadjuvant chemoimmunotherapy: a multicenter real-world study
Chunji Chen, Ziqiang Tian, Jiangbo Lin, Xuefeng Leng, Jianfei Shen, Jinbo Zhao, Huilai Lv, Changchun Wang, Xinyu Mei, Yongtao Han, Qifeng Wang, Jiahua Lv, Hainan Chen, Xiaolong Yan, Zhichao Liu, Zhengyang Zhang, Qing Zhong, Youhua Jiang, Liwei Xu, Xiaoyang Li, Dong Qian, Dehua Ma, Minhua Ye, Chunguo Wang, Zimin Wang, Zhigang Li, Xufeng Guo
Abstract
BACKGROUND: Although adjuvant immunotherapy demonstrated an improvement in disease-free survival (DFS) within the chemoradiotherapy cohort of the CheckMate 577 trial, its efficacy and role following NCIT remain to be elucidated. This large-sample, multicenter, real-world study aims to assess survival benefits of adjuvant immunotherapy in esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant chemoimmunotherapy (NCIT) followed by R0 resection. METHODS: This multicenter retrospective study (eight centers, January 2019-March 2023) included 724 ESCC patients undergoing NCIT and R0 resection. Propensity score matching (PSM) balanced 262 patients per group: NCIT + Surgery (NCIT + S) vs. NCIT + Surgery + adjuvant immunotherapy [NCIT + S + ICI (immune checkpoint inhibitors)]. Primary endpoints were 2-year overall survival (OS) and DFS; secondary endpoints included recurrence patterns. FINDINGS: Median follow-up: 31.2 months (IQR 24.0-39.9). Post-PSM analysis showed no significant OS benefit [2-year OS: 80.0% vs. 84.5%, hazard ratio (HR) = 1.15, 95% confidence interval (CI): 0.78-1.70, P = 0.12] or DFS improvement (77.7% vs. 72.6%, HR = 0.97, 95% CI: 0.69-1.37, P = 0.69) for NCIT + S vs. NCIT + S + ICI. Adjuvant immunotherapy was not independently protective for OS (HR = 0.87, P = 0.48) or DFS (HR = 1.03, P = 0.87). However, subgroup analyses revealed OS benefits in Non-MPR (major pathological response) patients (63.9% vs. 81.7%, HR = 1.78, 95% CI: 1.05-3.03, P = 0.035) and non- pathological complete response (pCR) patients (74.9% vs. 84.3%, HR = 1.39, 95% CI: 1.19-2.10, P = 0.031). Recurrence rates did not differ (local: 15.3% vs. 20.2%, P = 0.50; distant: 16.8% vs. 21.6%, P = 0.17). INTERPRETATION: Adjuvant immunotherapy provided no survival benefit in the overall NCIT-treated ESCC cohort but improved OS in patients with residual tumor (Non-MPR/Non-pCR). Further studies are warranted to refine patient selection for adjuvant immunotherapy in this setting.