编者按：2024年8月8日至10日，美国临床肿瘤学会亚洲突破峰会在日本横滨隆重举行。【医悦汇】带来由中国医学科学院肿瘤医院李印教授团队在本次大会上分享的《卡瑞利珠单抗联合化疗与单独化疗作为可切除食管鳞状细胞癌新辅助治疗（ESCORT-NEO）:一项多中心、随机III期试验》。

正文如下

卡瑞利珠单抗联合化疗与单独化疗作为可切除食管鳞状细胞癌新辅助治疗（ESCORT-NEO）:一项多中心、随机III期试验

Chemotherapy plus camrelizumab versus chemotherapy alone as neoadjuvant treatment for resectable esophageal squamous cell carcinoma (ESCORT-NEO): A multi-center, randomized phase III trial.

背景

新辅助化疗或放化疗后手术是可切除的局部晚期食管鳞状细胞癌（LA-ESCC）的标准治疗。然而，手术后复发仍是一个令人关注的问题。最近单臂研究显示，新辅助camrelizumab（一种PD-1抑制剂）联合化疗显示出有希望的结果。这项多中心、随机、开放标签、III期研究旨在评估新辅助camrelizumab联合化疗后继以辅助camrelizumab，与单独新辅助化疗相比，对可切除LA-ESCC的作用。

Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is the standard of care for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, recurrence post-surgery remains a concern. Recent single-arm studies with neoadjuvant camrelizumab plus chemotherapy showed promising results. This multicenter, randomized, open-label, phase III study aims to evaluate the role of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, versus neoadjuvant chemotherapy alone for resectable LA-ESCC.

方法

可切除的胸段LA-ESCC患者（T1b-3N1-3M0或T3N0M0）根据临床分期（I/II、III或IVa）分层，并随机（1:1:1）分为三组，进行两个3周周期的新辅助治疗。A组接受camrelizumab、白蛋白结合型紫杉醇和顺铂；B组使用camrelizumab、紫杉醇和顺铂；C组接受紫杉醇和顺铂。计划在新辅助治疗后4-6周进行手术。术后辅助camrelizumab每3周给予A和B组，最多15个周期。共同主要终点是病理完全缓解（pCR）率，由独立盲法病理委员会评估，以及无事件生存期，由研究者根据RECIST 1.1评估。使用图形方法控制整体I型错误在主要终点的单侧0.025。

Patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified according to clinical stage (I/II, III, or IVa) and randomized (1:1:1) to three groups for two 3-week cycles of neoadjuvant therapy. Group A received camrelizumab, albumin-bound paclitaxel and cisplatin; group B used camrelizumab, paclitaxel and cisplatin; group C received paclitaxel and cisplatin. Surgery was planned 4-6 weeks post-neoadjuvant therapy. Postoperative adjuvant camrelizumab every 3 weeks was given to groups A and B for up to 15 cycles. The co-primary endpoints were pathological complete response (pCR) rate, assessed by an independent blinded pathological committee, and event-free survival, evaluated by investigators per RECIST 1.1. The overall type I error was controlled at a one-sided 0.025 across the primary endpoints using a graphical method.

结果

从2021年4月至2023年8月，我们招募了391名患者：A组（n = 132）、B组（n = 130）和C组（n = 129）。临床分期I/II、III和IVa的患者分别为106（27.1%）、279（71.4%）和6（1.5%）。肿瘤位于上、中、下胸段食管的患者分别为41（10.5%）、201（51.4%）和149（38.1%）。来自A、B和C组的128（97.0%）、125（96.2%）和122（94.6%）名患者完成了两个周期的新辅助治疗，114（86.4%）、116（89.2%）和103（79.8%）接受了手术。在意向治疗人群中，A组（28.0%）和B组（15.4%）的pCR率显著高于C组（4.7%）（A组与C组：差异，23.5%，95%CI，15.1-32.0；OR，8.11，95%CI，3.28-20.06；双侧P < 0.0001；B组与C组：差异，10.9%，95%CI，3.7-18.1；OR，3.81，95%CI，1.48-9.80；双侧P = 0.0034）；主要病理反应率分别为A、B和C组的59.1%、36.2%和20.9%。在手术组中，A、B和C组的R0切除率分别为99.1%、95.7%和92.2%，术后并发症的发生率分别为34.2%、38.8%和32.0%。在新辅助治疗期间，≥3级治疗相关不良事件的发生率分别为34.1%、28.5%和28.8%。

Between April, 2021, and August, 2023, we enrolled 391 patients: group A (n = 132), group B (n = 130), and group C (n = 129). 106 (27.1%), 279 (71.4%), 6 (1.5%) patients were in clinical stage I/II, III, and IVa. Tumors were located in the upper, middle, and lower thoracic esophagus for 41 (10.5%), 201 (51.4%), and 149 (38.1%) patients. 128 (97.0%), 125 (96.2%), and 122 (94.6%) patients from groups A, B, and C completed two cycles of neoadjuvant therapy, and 114 (86.4%), 116 (89.2%), and 103 (79.8%) underwent surgery. In the intention-to-treat population, the pCR rate was significantly higher in groups A (28.0%) and B (15.4%) compared to group C (4.7%) (group A vs. C: difference, 23.5%, 95%CI, 15.1-32.0; OR, 8.11, 95%CI, 3.28-20.06; two-sided P < 0.0001; group B vs. C: difference, 10.9%, 95%CI, 3.7-18.1; OR, 3.81, 95%CI, 1.48-9.80; two-sided P = 0.0034); major pathologic response rates were 59.1%, 36.2%, 20.9% for groups A, B and C. In the surgical set, the R0 resection rate was 99.1%, 95.7% and 92.2% for groups A, B and C, and the incidence of postoperative complications was 34.2%, 38.8% and 32.0%. During neoadjuvant treatment, the incidence of grade ≥3 treatment-related adverse events was 34.1%, 28.5% and 28.8%.

结论

在可切除的LA-ESCC患者中，与单独新辅助化疗相比，新辅助camrelizumab联合化疗显示出更高的pCR率和可接受的安全性。临床试验信息：ChiCTR2000040034。

In resectable LA-ESCC patients, neoadjuvant camrelizumab with chemotherapy showed superior pCR and a tolerable safety profile compared to neoadjuvant chemotherapy alone. Clinical trial information: ChiCTR2000040034.

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