Toripalimab Plus Paclitaxel and Carboplatin as Neoadjuvant Therapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma. (28th January 2022)

• Record Type: Journal Article
• Authors: He, Wenwu; Leng, Xuefeng; Mao, Tianqin; Luo, Xi; Zhou, Lingxiao; Yan, Jiaxin; Peng, Lin; Fang, Qiang; Liu, Guangyuan; Wei, Xing; Wang, Kangning; Wang, Chenghao; Zhang, Sha; Zhang, Xudong; Shen, Xudong; Huang, Depei; Yi, Huan; Bei, Ting; She, Xueke; Xiao, Wenguang; Han, Yongtao
• Is Part Of: Oncologist. Volume 27:Number 1(2022)
• Page Start: e18
• Page End: e28
• Publication Date: 2022-01-28
• Subjects: esophageal squamous cell carcinoma -- neoadjuvant therapy -- toripalimab -- chemotherapy; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1093/oncolo/oyab011
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: 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/m 2, 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 ( P = .036) in responders upon neoadjuvant therapy. Responders were associated with higher baseline gene expression levels of CXCL5 ( P = .03) and lower baseline levels of CCL19 ( P = .017) and UMODL1 ( P = .03). Conclusions: The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC, indicating its potential as a neoadjuvant treatment for ESCC. Clinical Trial registration: NCT04177797 Abstract : This article reports on the safety, feasibility, and efficacy of toripalimab (a PD-1 antibody) combined with paclitaxel and carboplatin for locally advanced resectable esophageal squamous cell carcinoma in the neoadjuvant setting.