Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Department of Radiotherapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Eur J Cancer. 2021 Feb;144:232-241. doi: 10.1016/j.ejca.2020.11.039. Epub 2020 Dec 26.
To investigate the safety and activity of preoperative pembrolizumab combined with chemoradiotherapy for resectable oesophageal squamous cell carcinoma (ESCC) (ClinicalTrials.gov number, NCT03792347).
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, 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.
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).
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).
为了探究术前帕博利珠单抗联合放化疗治疗可切除食管鳞癌（ESCC）的安全性和活性（ClinicalTrials.gov 编号：NCT03792347）。
20 例可切除 ESCC 患者，无论程序性死亡配体-1 状态如何，均接受术前帕博利珠单抗联合放化疗（PPCT）。术前治疗包括卡铂（曲线下面积 2 毫克/毫升/分钟，每周一次，共 5 周）、紫杉醇（50mg/m，每周一次，共 5 周）、放疗（23 次 1.8Gy，每周 5 次）和帕博利珠单抗（2mg/kg），于第 1 天和第 22 天给药。术前治疗后 4-6 周内，患者行手术治疗。主要终点为安全性，次要终点为可行性、病理完全缓解（pCR）率和影像学反应。采用免疫组化和免疫荧光法评估手术标本中 CD8 T 细胞的免疫特征。
除 1 例患者因白细胞减少而错过最后一剂化疗外，所有患者均成功接受了 PPCT 治疗。13 例（13/20，65%）患者出现 3 级及以上不良事件（AE），1 例患者出现 5 级 AE。最常见的 3 级 AE 为淋巴细胞减少（12/13，92%）。18 例患者在 PPCT 后 4-9 周内接受手术，pCR 率为 55.6%（10/18）。pCR 组转录因子 1 阳性细胞的百分比明显高于非 pCR 组（p 值=0.010）。
PPCT 安全，不延迟手术，并使 55.6%的切除肿瘤达到 pCR。一项多中心 II 期研究正在进行中，以进一步证实疗效（NCT04435197）。
