Zhou Na, Hua Yuwei, Ge Yuping, Wang Qiang, Wang Chenyu, He Jia, Zhao Luo, Yu Shuangni, Yan Junfang, Zhao Lin, Li Li, Bai Chunmei
Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, China.
Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China.
Front Immunol. 2024 Dec 2;15:1482005. doi: 10.3389/fimmu.2024.1482005. eCollection 2024.
The application of neoadjuvant immunotherapy in the treatment of esophageal cancer needs further exploration. This study aimed to investigate the safety and effectiveness of tislelizumab, an anti-PD-1 antibody, combined with chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC).
In this phase II study, patients with clinical stages of II-IVA (T3-T4 and/or node positive) potentially resectable LA-ESCC were enrolled. Patients received neoadjuvant tislelizumab and chemotherapy every 3 weeks for 4 cycles before surgery and adjuvant tislelizumab for 9 months. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included R0 resection, disease free survival (DFS), adverse events (AE), and biomarkers for predicting efficacy.
The study included 30 patients. 25 patients completed neoadjuvant chemoimmunotherapy and underwent surgery, 96% with R0 resection. The pCR and MPR rate was 44% and 52%. The 6-month and 1-year DFS rate was 100% and 75.3%. 43.3% patients experienced severe (grade 3-4) treatment-related adverse events (TRAEs) and 5 patients developed severe immune-related adverse events (irAEs). Further exploration found that a group of peripheral lymphocyte subsets increased significantly after 2 cycles of neoadjuvant therapy in patients who achieved pCR, suggesting the importance of dynamic monitoring of circulating lymphocyte.
The combination of perioperative tislelizumab and neoadjuvant chemotherapy has achieved an encouraging pCR rate and demonstrated a manageable safety profile in patients with potentially resectable ESCC.
https://www.chictr.org.cn/, identifier ChiCTR2100043772.
新辅助免疫疗法在食管癌治疗中的应用有待进一步探索。本研究旨在探讨抗程序性死亡蛋白1（PD-1）抗体替雷利珠单抗联合化疗作为局部晚期食管鳞状细胞癌（LA-ESCC）新辅助治疗的安全性和有效性。
在这项II期研究中，纳入临床分期为II-IVA期（T3-T4和/或淋巴结阳性）且可能可切除的LA-ESCC患者。患者在手术前每3周接受新辅助替雷利珠单抗和化疗，共4个周期，术后接受辅助替雷利珠单抗治疗9个月。主要终点为病理完全缓解（pCR）率。次要终点包括R0切除、无病生存期（DFS）、不良事件（AE）以及预测疗效的生物标志物。
该研究共纳入30例患者。25例患者完成新辅助化疗联合免疫治疗并接受手术，R0切除率为96%。pCR率和主要病理缓解（MPR）率分别为44%和52%。6个月和1年DFS率分别为100%和75.3%。43.3%的患者发生严重（3-4级）治疗相关不良事件（TRAEs），5例患者发生严重免疫相关不良事件（irAEs）。进一步探索发现，达到pCR的患者在新辅助治疗2个周期后，一组外周淋巴细胞亚群显著增加，提示动态监测循环淋巴细胞的重要性。
围手术期替雷利珠单抗联合新辅助化疗在可切除ESCC患者中取得了令人鼓舞的pCR率，且安全性可控。
