Department of Thoracic Surgery, Sichuan Cancer Hospital and Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China.
School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, People's Republic of China.
Oncologist. 2022 Feb 3;27(1):e18-e28. doi: 10.1093/oncolo/oyab011.
Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data.
In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m2, day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in each 3-week cycle for 2 cycles, followed by esophagectomy planned 4-6 weeks after preoperative therapy. The primary endpoints were safety, feasibility, and the major pathological response (MPR) rate; the secondary endpoints were the pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS). Association between molecular signatures/tumor immune microenvironment and treatment response was also explored.
Twenty resectable ESCC patients were enrolled. Treatment-related adverse events (AEs) occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related AEs. Sixteen patients underwent surgery without treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Among the 16 patients, the MPR rate was 43.8% (7/16) and the pCR rate was 18.8% (3/16). The abundance of CD8+ T cells in surgical specimens increased (P = .0093), accompanied by a decreased proportion of M2-type tumor-associated macrophages (P = .036) in responders upon neoadjuvant therapy. Responders were associated with higher baseline gene expression levels of CXCL5 (P = .03) and lower baseline levels of CCL19 (P = .017) and UMODL1 (P = .03).
The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC, indicating its potential as a neoadjuvant treatment for ESCC.
NCT04177797.
免疫检查点抑制剂（ICIs）在治疗晚期食管鳞状细胞癌（ESCC）方面具有显著疗效；然而，它们在局部晚期可切除 ESCC 中的疗效以及潜在的预测生物标志物的数据有限。
本研究纳入了局部晚期可切除的 ESCC 患者，接受新辅助替雷利珠单抗（240mg，第 1 天）联合紫杉醇（135mg/m2，第 1 天）和卡铂（AUC 为 5mg/mL/min，第 1 天），每 3 周为一个周期，共 2 个周期，然后在术前治疗后 4-6 周进行食管切除术。主要终点是安全性、可行性和主要病理缓解（MPR）率；次要终点是病理完全缓解（pCR）率、无病生存期（DFS）和总生存期（OS）。还探索了分子特征/肿瘤免疫微环境与治疗反应之间的关系。
共纳入 20 例可切除的 ESCC 患者。所有患者（100%）均发生与治疗相关的不良事件（AE），4 例（22.2%）患者发生 3 级或以上与治疗相关的 AE。16 例患者接受了手术，没有因治疗相关的手术延迟，R0 切除率为 87.5%（14/16）。在 16 例患者中，MPR 率为 43.8%（16/16），pCR 率为 18.8%（16/16）。新辅助治疗后，手术标本中 CD8+T 细胞的丰度增加（P=.0093），同时 M2 型肿瘤相关巨噬细胞的比例降低（P=.036）。应答者的基线 CXCL5 基因表达水平较高（P=.03），CCL19 和 UMODL1 的基线水平较低（P=.017 和 P=.03）。
替雷利珠单抗联合紫杉醇和卡铂在局部晚期可切除 ESCC 中安全、可行且有效，表明其具有作为 ESCC 新辅助治疗的潜力。
NCT04177797。
