Toripalimab Plus Paclitaxel and Carboplatin as Neoadjuvant Therapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

作者：Wenwu He, Xuefeng Leng, Tianqin Mao, Xi Luo, Lingxiao Zhou, Jiaxin Yan, Lin Peng, Qiang Fang, Guangyuan Liu, Xing Wei, Kangning Wang, Chenghao Wang, Sha Zhang, Xudong Zhang, Xudong Shen, Depei Huang, Huan Yi, Ting Bei, Xueke She, Wenguang Xiao, Yongtao Han · 发表于：The Oncologist · 年份：2022 · DOI：10.1093/oncolo/oyab011 · 被引用次数：105 · 研究领域：Esophageal Cancer Research and Treatment、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data. METHODS: In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m2, day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in each 3-week cycle for 2 cycles, followed by esophagectomy planned 4-6 weeks after preoperative therapy. The primary endpoints were safety, feasibility, and the major pathological response (MPR) rate; the secondary endpoints were the pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS). Association between molecular signatures/tumor immune microenvironment and treatment response was also explored. RESULTS: Twenty resectable ESCC patients were enrolled. Treatment-related adverse events (AEs) occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related AEs. Sixteen patients underwent surgery without treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Among the 16 patients, the MPR rate was 43.8% (7/16) and the pCR rate was 18.8% (3/16). The abundance of CD8+ T cells in surgical specimens increased (P = .0093), accompanied by a decreased proportion of M2-type tumor-associated macrophages ...