Neoadjuvant sintilimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, single-center, phase 2 trial (ESONICT-1).
Neoadjuvant sintilimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, single-center, phase 2 trial (ESONICT-1).
复制标题
DOI：
10.21037/atm-21-5381
复制
发表时间：
2021-11
影响因子：
--
通讯作者：
Kang M
中科院分区：
文献类型：
--
作者：
Zhang Z;Hong ZN;Xie S;Lin W;Lin Y;Zhu J;Yang X;Lin Z;Lin J;Kang M
探讨新辅助药物欣替单抗联合化疗治疗局部晚期食管鳞状细胞癌（ESCC）的安全性和可行性。该研究是一项研究者发起的、开放标签、非随机、单组、单中心的2期临床试验。年龄在18至75岁之间的局部晚期ESCC患者符合新辅助免疫化疗（nICT）的条件。nICT包括顺铂（60 mg/m2）在第1天，白蛋白结合紫杉醇（125 mg/m2）在第1天和第8天，辛替单抗（200 mg）在每21天周期的第1天。nICT治疗2个周期后进行临床评价。nICT术后4-6周内，患者行食管切除术。主要终点为病理完全缓解（pCR）和不良事件（ae）。次要终点包括主要病理反应（MPR）、R0切除率、手术间隔时间和30天并发症。本试验注册号为chictr.org.cn，注册号为ChiCTR2100045659。从2020年7月到2021年6月，30名患者入组。所有患者均成功完成2个周期的nICT治疗。nICT期间AE很常见，最常见的AE是厌食症（20/ 30,67 %）。然而，只有1例3级ESCC患者转氨酶升高。经影像学评价，客观有效率（ORR）为67%(20/30)，疾病控制率为97%（29/30）。23例患者行McKeown微创食管切除术（MIE）。原发肿瘤的pCR率为21.7%，原发肿瘤的MPR率为52.2%。中位手术间隔为40天，无患者因不良事件延迟手术。肺炎是最常见的术后30天主要并发症（9/23,39%）。2例患者在住院期间发生吻合口漏（AL）， 1例患者因AL再次入院。无治疗或手术相关死亡。新辅助辛替单抗联合化疗治疗局部晚期ESCC安全可行，ae有限，R0切除率高，pCR率有希望，术后并发症可控。需要长期随访。一项多中心、随机、III期临床试验评估了sintilimab与安慰剂联合化疗治疗局部晚期ESCC的有效性和安全性，以证实这些结果。
To investigate the safety and feasibility of combining neoadjuvant sintilimab (Innovent Biologics, Suzhou, China) and chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC). The study was an investigator-initiated, open-label, non-randomized, single-arm, single-center phase 2 trial. Patients aged between 18 to 75 years with locally advanced ESCC were eligible for neoadjuvant immunochemotherapy (nICT). The nICT included cisplatin (60 mg/m2) on day 1, albumin-bound paclitaxel (125 mg/m2) on days 1 and 8, and sintilimab (200 mg) on day 1 of each 21-day cycle. Clinical evaluation was conducted after 2 cycles of nICT. Within 4–6 weeks after nICT, patients underwent esophagectomy. The primary end points were pathological complete response (pCR) and adverse events (AEs). Secondary endpoints included major pathological response (MPR), R0 resection rate, interval to surgery, and 30-day complications. This trial was registered at chictr.org.cn, ChiCTR2100045659. From July 2020 to June 2021, 30 patients were enrolled. All patients successfully completed 2 cycles of nICT. AEs were common during nICT, and the most common AE was anorexia (20/30, 67%). However, only one patient with grade 3 ESCC had increased transaminase. According to radiologic evaluations, the objective response rate (ORR) was 67% (20/30) and the disease control rate 97% (29/30). Twenty-three patients underwent McKeown minimally invasive esophagectomy (MIE). The pCR rate of the primary tumor was 21.7%, and the MPR rate of the primary tumor was 52.2%. The median interval to surgery was 40 days, and no patients delayed surgery due to AEs. Pneumonia was the most common major 30-day postoperative complication (9/23, 39%). Anastomotic leakage (AL) occurred in two patients during the hospital stay, and one patient was readmitted due to AL. There was no treatment- or surgery-related deaths. Neoadjuvant sintilimab plus chemotherapy for locally advanced ESCC appears to be safe and feasible with limited AEs, high R0 resection rate, promising pCR rate, and manageable postoperative complications. Long-term follow-up is required. A multicenter, randomized, phase III clinical trial assessing the efficacy and safety of sintilimab versus placebo in combination with chemotherapy in locally advanced ESCC is warranted to confirm these results.