Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, P. R. China.
Department of Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, P. R. China.
Cancer Commun (Lond). 2024 Oct;44(10):1214-1227. doi: 10.1002/cac2.12604. Epub 2024 Sep 2.
In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE.
A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m) + cisplatin (75 mg/m) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed.
Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%).
The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.
在免疫治疗时代，新辅助免疫化疗（NAIC）用于治疗局部晚期食管鳞状细胞癌（ESCC）已在临床上应用，但缺乏高级别的临床证据。本研究旨在比较纳武利尤单抗联合紫杉醇和卡铂（NAIC）新辅助治疗后微创食管切除术（MIE）与单纯新辅助化疗（NAC）新辅助治疗后 MIE 的安全性和长期疗效。
本研究为一项在中国河南肿瘤医院进行的前瞻性、单中心、开放性、随机 III 期临床试验。患者被随机分配接受纳武利尤单抗（240 mg）联合紫杉醇（175 mg/m）+顺铂（75 mg/m）（纳武利尤单抗组）或紫杉醇+顺铂（化疗组），每 3 周治疗 2 个周期。手术后，纳武利尤单抗组接受纳武利尤单抗（每 3 周 240 mg，持续 6 个月）。主要终点是无事件生存（EFS）。病理完全缓解（pCR）和总生存（OS）是关键次要终点。还评估了不良事件（AE）和生活质量。
2020 年 5 月 15 日至 2021 年 8 月 13 日，共纳入 252 例 T1N1-3M0 至 T2-3N0-3M0 期 ESCC 患者进行中期分析，纳武利尤单抗组 127 例，化疗组 125 例。纳武利尤单抗组的 1 年 EFS 率为 77.9%，化疗组为 64.3%（风险比[HR] = 0.62；95%置信区间[CI] = 0.39 至 1.00；P = 0.05）。纳武利尤单抗组和化疗组的 1 年 OS 率分别为 94.1%和 83.0%（HR = 0.48；95%CI = 0.24 至 0.97；P = 0.037）。纳武利尤单抗组的 pCR 率更高（18.6% vs. 4.6%；P = 0.001）。纳武利尤单抗组术后 Clavien-Dindo 分级 IIIb 或更高发病率为 9.8%，化疗组为 6.8%，差异无统计学意义（P = 0.460）。两组治疗相关 3 级或 4 级不良事件发生率无差异（12.5%与 12.4%）。
这项正在进行的试验的中期结果表明，在可切除的 ESCC 中，围手术期添加纳武利尤单抗联合 NAC 是安全的，可能改善 OS 并可能改变未来的标准治疗。
