Chen Rui, Liu Qianwen, Li Qiaoqiao, Zhu Yujia, Zhao Lei, Liu Shiliang, Chen Baoqing, Liu Mengzhong, Hu Yonghong, Lin Ting, Li Jibin, Chen Jiyang, Lv Yingxin, Fu Jianhua, Xi Mian, Yang Hong
State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China.
Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
EClinicalMedicine. 2023 Jul 26;62:102118. doi: 10.1016/j.eclinm.2023.102118. eCollection 2023 Aug.
To evaluate the efficacy and safety of toripalimab combined with neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (ESCC).
In this single arm, phase II trial, 44 ESCC patients were enrolled from December 2019 to July 2021 at Sun Yat-sen University Cancer Center (Guangzhou, China). All patients received concurrent radiotherapy (44 Gy in 20 fractions), chemotherapy (paclitaxel 50 mg/m and cisplatin 25 mg/m on days 1, 8, 15, and 22), and toripalimab (240 mg on days 1 and 22). Within 6-8 weeks of neoadjuvant treatment, patients underwent surgery. The results of the study patients were compared with those of 86 matched patients between July 2015 and March 2022. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoints were treatment-related adverse events and R0 rates. This trail was registered with ClinicalTrails.gov, NCT04006041.
All patients received neoadjuvant treatment, and 42 completed esophagectomy. Of the 42 patients, 21 (50%; 95% CI 35-65) achieved pCR and 2 (5%) patients were ypT0N+. The R0 resection rate was 98% (41/42). Nine (20%) of 44 patients had grade 3/4 adverse events. Among the perioperative complications (n = 42), anastomotic leakage occurred in five cases (12%), tracheal fistula in three cases (7%), and postoperative death in one case (2%) due to tracheal fistula. Compared with the control cohort, the pCR rate of the study group was higher but without significant difference (50% vs. 36%, = 0.19).
Toripalimab combined with NCRT failed to show significantly better pCR rate than historical data. Nevertheless, considering the signs of efficacy and acceptable safety of this regimen, further evaluation in phase III randomized trials might be warranted.
National Natural Science Foundation of China.
评估特瑞普利单抗联合新辅助放化疗（NCRT）治疗局部晚期食管鳞状细胞癌（ESCC）的疗效和安全性。
在这项单臂II期试验中，2019年12月至2021年7月期间，中山大学肿瘤防治中心（中国广州）招募了44例ESCC患者。所有患者均接受同步放疗（20次分割，共44 Gy）、化疗（第1、8、15和22天给予紫杉醇50 mg/m和顺铂25 mg/m）以及特瑞普利单抗（第1天和第22天给予240 mg）。在新辅助治疗的6 - 8周内，患者接受手术。将研究患者的结果与2015年7月至2022年3月期间86例匹配患者的结果进行比较。主要终点为病理完全缓解（pCR）率，次要终点为治疗相关不良事件和R0切除率。该试验已在ClinicalTrails.gov注册，注册号为NCT04006041。
所有患者均接受了新辅助治疗，42例完成了食管切除术。在这42例患者中，21例（50%；95%CI 35 - 65）达到pCR，2例（5%）患者为ypT0N +。R0切除率为98%（41/42）。44例患者中有9例（20%）发生3/4级不良事件。在围手术期并发症（n = 42）中，5例（12%）发生吻合口漏，3例（7%）发生气管瘘，1例（2%）因气管瘘术后死亡。与对照组相比，研究组的pCR率更高，但无显著差异（50%对36%，P = 0.19）。
特瑞普利单抗联合NCRT未能显示出比历史数据显著更好的pCR率。然而，考虑到该方案的疗效迹象和可接受的安全性，可能有必要在III期随机试验中进行进一步评估。
中国国家自然科学基金。
