PMID- 33373868 OWN - NLM STAT- MEDLINE DCOM- 20210917 LR - 20210917 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 144 DP - 2021 Feb TI - Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). PG - 232-241 LID - S0959-8049(20)31376-9 [pii] LID - 10.1016/j.ejca.2020.11.039 [doi] AB - BACKGROUND: To investigate the safety and activity of preoperative pembrolizumab combined with chemoradiotherapy for resectable oesophageal squamous cell carcinoma (ESCC) (ClinicalTrials.gov number, NCT03792347). METHODS: Twenty resectable ESCC patients, regardless of programmed death ligand-1 status, received preoperative pembrolizumab with concurrent chemoradiotherapy (PPCT). Preoperative therapy includes carboplatin (area under the curve of 2 mg per milliliter per minute, once a week for 5 weeks), paclitaxel (50 mg/m(2), once a week for 5 weeks), radiotherapy (23 fractions of 1.8 Gy, 5 fraction a week) and pembrolizumab (2 mg/kg) on days 1 and 22. Within 4-6 weeks after preoperative therapy, patients underwent surgery. The primary end-point was safety and secondary outcome measures were feasibility, pathologic complete response (pCR) rate and radiographic response. Immune signature of CD8(+) T cells was evaluated in surgical specimens using immunohistochemistry and immunofluorescence. RESULTS: All patients have received PPCT successfully, except one patient who missed the last dose of chemotherapy due to leukopenia. Grade III and higher adverse events (AEs) were observed in 13 patients (13/20, 65%), and one patient had a grade V AE. The most frequent grade III AE was lymphopenia (12/13, 92%). Eighteen patients underwent surgery within 4-9 weeks after PPCT and the pCR rate was 55.6% (10/18). The percentage of transcription factor 1 positive cells was significantly higher in specimens of pCR group than those of non-pCR group (p value = 0.010). CONCLUSIONS: PPCT was safe, did not delay surgery, and induced a pCR in 55.6% of resected tumours. A phase II multicentre study is undergoing for further confirmation of efficacy (NCT04435197). CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Li, Chengqiang AU - Li C AD - Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Zhao, Shengguang AU - Zhao S AD - Department of Radiotherapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Zheng, Yuyan AU - Zheng Y AD - Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Han, Yichao AU - Han Y AD - Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Chen, Xiaoyan AU - Chen X AD - Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Cheng, Zenghui AU - Cheng Z AD - Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Wu, Yuquan AU - Wu Y AD - Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Feng, Xijia AU - Feng X AD - Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Qi, Weixiang AU - Qi W AD - Department of Radiotherapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Chen, Kai AU - Chen K AD - Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Xiang, Jie AU - Xiang J AD - Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Li, Jian AU - Li J AD - Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. FAU - Lerut, Toni AU - Lerut T AD - Department of Thoracic Surgery, University Hospital Leuven, Herestraat 49, 3000, Leuven, Belgium. FAU - Li, Hecheng AU - Li H AD - Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address: lihecheng2000@hotmail.com. LA - eng SI - ClinicalTrials.gov/NCT04435197 SI - ClinicalTrials.gov/NCT03792347 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201226 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Antibodies, Monoclonal, Humanized) RN - BG3F62OND5 (Carboplatin) RN - DPT0O3T46P (pembrolizumab) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Adult MH - Aged MH - Antibodies, Monoclonal, Humanized/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carboplatin/administration & dosage MH - Chemoradiotherapy/*mortality MH - Combined Modality Therapy MH - Esophageal Neoplasms/pathology/*therapy MH - Esophageal Squamous Cell Carcinoma/pathology/*therapy MH - Esophagectomy/*mortality MH - Female MH - Follow-Up Studies MH - Humans MH - Male MH - Middle Aged MH - Paclitaxel/administration & dosage MH - *Preoperative Care MH - Prognosis MH - Survival Rate OTO - NOTNLM OT - Chemoradiotherapy OT - Oesophageal squamous cell carcinoma OT - PD-1 inhibitor OT - Pathologic complete response COIS- Conflict of interest statement None declared. EDAT- 2020/12/30 06:00 MHDA- 2021/09/18 06:00 CRDT- 2020/12/29 20:10 PHST- 2020/06/28 00:00 [received] PHST- 2020/10/28 00:00 [revised] PHST- 2020/11/24 00:00 [accepted] PHST- 2020/12/30 06:00 [pubmed] PHST- 2021/09/18 06:00 [medline] PHST- 2020/12/29 20:10 [entrez] AID - S0959-8049(20)31376-9 [pii] AID - 10.1016/j.ejca.2020.11.039 [doi] PST - ppublish SO - Eur J Cancer. 2021 Feb;144:232-241. doi: 10.1016/j.ejca.2020.11.039. Epub 2020 Dec 26.