Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1)
Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1)
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术前派姆单抗联合放化疗治疗食管鳞癌（PALACE-1）
DOI：
10.1016/j.ejca.2020.11.039
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发表时间：
2021-02-01
影响因子：
8.4
通讯作者：
Li, Hecheng
中科院分区：
文献类型：
--
作者：
Li, Chengqiang;Zhao, Shengguang;Li, Hecheng
背景资料：研究术前派姆单抗联合放化疗治疗可切除食管鳞状细胞癌（ESCC）的安全性和活性（ClinicalTrials.gov编号，NCT 03792347）。方法：20例可切除ESCC患者，无论程序性死亡配体-1状态如何，均接受术前派姆单抗联合放化疗（PPCT）。术前治疗包括卡铂（2 mg/ml/min的曲线下面积，每周一次，持续5周）、紫杉醇（50 mg/m2，每周一次，持续5周）、放疗（23次，每次1.8戈伊，每周5次）和帕博利珠单抗（2 mg/kg），第1天和第22天。在术前治疗后4-6周内，患者接受手术。主要终点是安全性，次要结局指标是可行性、病理完全缓解（pCR）率和放射学缓解。结果：除1例患者因白细胞减少而错过最后一次化疗外，其余患者均成功接受PPCT治疗。在13例患者（13/20，65%）中观察到III级及以上不良事件（AE），1例患者发生V级AE。最常见的III级AE为淋巴细胞减少症（12/13，92%）。术后4-9周手术18例，pCR率55.6%（10/18）。转录因子1阳性细胞的百分比是显着较高的标本中的pCR组比non-pCR组（p值= 0.010）。结论：PPCT是安全的，不延迟手术，并诱导pCR在55.6%的切除肿瘤。正在进行一项II期多中心研究，以进一步确认疗效（NCT 04435197）。(C)2020爱思唯尔有限公司保留所有权利。
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). (C) 2020 Elsevier Ltd. All rights reserved.