PMID- 35305102 OWN - NLM STAT- MEDLINE DCOM- 20220420 LR - 20220420 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 27 IP - 1 DP - 2022 Feb 3 TI - Toripalimab Plus Paclitaxel and Carboplatin as Neoadjuvant Therapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma. PG - e18-e28 LID - 10.1093/oncolo/oyab011 [doi] AB - 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 (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. CI - (c) The Author(s) 2022. Published by Oxford University Press. FAU - He, Wenwu AU - He W AUID- ORCID: 0000-0002-2477-9587 AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Leng, Xuefeng AU - Leng X AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Mao, Tianqin AU - Mao T AD - School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Luo, Xi AU - Luo X AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Zhou, Lingxiao AU - Zhou L AD - Department of Endoscopy Center, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Yan, Jiaxin AU - Yan J AD - Department of Pathology, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Peng, Lin AU - Peng L AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Fang, Qiang AU - Fang Q AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Liu, Guangyuan AU - Liu G AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Wei, Xing AU - Wei X AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Wang, Kangning AU - Wang K AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Wang, Chenghao AU - Wang C AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Zhang, Sha AU - Zhang S AD - Department of Endoscopy Center, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Zhang, Xudong AU - Zhang X AD - Department of Drug Clinical Trial, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Shen, Xudong AU - Shen X AD - The Medical Department, 3D Medicines Inc., Shanghai, People's Republic of China. FAU - Huang, Depei AU - Huang D AD - The Medical Department, 3D Medicines Inc., Shanghai, People's Republic of China. FAU - Yi, Huan AU - Yi H AD - The Medical Department, 3D Medicines Inc., Shanghai, People's Republic of China. FAU - Bei, Ting AU - Bei T AD - The Medical Department, 3D Medicines Inc., Shanghai, People's Republic of China. FAU - She, Xueke AU - She X AD - Shanghai Junshi Biosciences Co., Ltd, Shanghai, People's Republic of China. FAU - Xiao, Wenguang AU - Xiao W AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. FAU - Han, Yongtao AU - Han Y AD - Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China. LA - eng SI - ClinicalTrials.gov/NCT04177797 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 8JXN261VVA (toripalimab) RN - BG3F62OND5 (Carboplatin) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use MH - Carboplatin/pharmacology/therapeutic use MH - *Esophageal Neoplasms/drug therapy/pathology/surgery MH - *Esophageal Squamous Cell Carcinoma/drug therapy/pathology/surgery MH - Humans MH - Neoadjuvant Therapy/adverse effects MH - Paclitaxel MH - Tumor Microenvironment PMC - PMC8842349 OTO - NOTNLM OT - chemotherapy OT - esophageal squamous cell carcinoma OT - neoadjuvant therapy OT - toripalimab EDAT- 2022/03/20 06:00 MHDA- 2022/04/21 06:00 PMCR- 2022/01/28 CRDT- 2022/03/19 17:07 PHST- 2021/05/21 00:00 [received] PHST- 2021/11/18 00:00 [accepted] PHST- 2022/03/19 17:07 [entrez] PHST- 2022/03/20 06:00 [pubmed] PHST- 2022/04/21 06:00 [medline] PHST- 2022/01/28 00:00 [pmc-release] AID - 6516578 [pii] AID - oyab011 [pii] AID - 10.1093/oncolo/oyab011 [doi] PST - ppublish SO - Oncologist. 2022 Feb 3;27(1):e18-e28. doi: 10.1093/oncolo/oyab011.