Gao Lei, Lu Jieming, Zhang Peipei, Hong Zhi-Nuan, Kang Mingqiang
Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China.
J Gastrointest Oncol. 2022 Apr;13(2):478-487. doi: 10.21037/jgo-22-131.
More and more evidence has confirmed the efficacy and safety of immunotherapy drugs, such as camrelizumab and pembrolizumab. There are several phase-I/II studies showing that toripalimab has an acceptable safety profile and promising clinical activity in patients with advanced solid tumors. To further confirm its efficacy and safety, the aim of the study was to evaluate toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC).
This study was an investigator-initiated, open-label, non-randomized, single-arm, single-center phase II trial (registration number: ChiCTR2100052784). The patients eligible for inclusion criteria at Fujian Medical University Union Hospital from October 2019 to October 2020 were included in this study. Patients who were suitable for surgery underwent minimally invasive esophagectomy (MIE) within 4-6 weeks after neoadjuvant therapy. Pathological complete response (pCR) and adverse events (AEs) were the primary end points. Secondary endpoints included R0 resection rate, major pathological response (MPR), interval to surgery, and 30-day complications.
A total of 20 patients were enrolled from October 2019 to October 2020. All patients successfully completed 2 cycles of neoadjuvant therapy. Treatment-related AEs were common during neoadjuvant therapy, with leucopenia the most frequently occurring AE (4/20, 25%). With respect to immune-related AEs, immune dermatitis occurred in 2 patients, including 1 patient with grade I and 1 patient with grade III. Based on radiologic evaluation, the objective response rate (ORR) was 70% (14/20). Twelve patients underwent McKeown MIE. The pCR rate of the primary tumor was 16.7% (2/12), and the MPR rate of the primary tumor was 5/12 (41.7%). The mean interval to surgery was 33.2 days, and no patients experienced delayed surgery due to treatment-related AEs. Pneumonia was the most common 30-day postoperative complication (3/12, 25%). Anastomotic leakage (AL) only occurred in 1 patient during the hospital stay. There were no treatment- or surgery-related deaths.
Based on our results, toripalimab combined with docetaxel and cisplatin as a novel neoadjuvant therapy was safe and effective in locally advanced ESCC.
越来越多的证据证实了免疫治疗药物的有效性和安全性，如卡瑞利珠单抗和帕博利珠单抗。多项I/II期研究表明，特瑞普利单抗在晚期实体瘤患者中具有可接受的安全性和有前景的临床活性。为进一步证实其有效性和安全性，本研究旨在评估特瑞普利单抗联合多西他赛和顺铂用于局部晚期食管鳞状细胞癌（ESCC）的新辅助治疗效果。
本研究是一项由研究者发起的、开放标签、非随机、单臂、单中心的II期试验（注册号：ChiCTR2100052784）。纳入2019年10月至2020年10月在福建医科大学附属协和医院符合纳入标准的患者。适合手术的患者在新辅助治疗后4 - 6周内行微创食管切除术（MIE）。病理完全缓解（pCR）和不良事件（AE）为主要终点。次要终点包括R0切除率、主要病理缓解（MPR）、手术间隔时间和30天并发症。
2019年10月至2020年10月共纳入20例患者。所有患者均成功完成2周期新辅助治疗。新辅助治疗期间治疗相关AE常见，白细胞减少是最常发生的AE（4/20，25%）。免疫相关AE方面，2例患者发生免疫性皮炎，其中1例为I级，1例为III级。基于影像学评估，客观缓解率（ORR）为70%（14/20）。12例患者接受了McKeown MIE。原发肿瘤的pCR率为16.7%（2/12），原发肿瘤的MPR率为5/12（41.7%）。平均手术间隔时间为33.2天，无患者因治疗相关AE而延迟手术。肺炎是最常见的术后30天并发症（3/12，25%）。住院期间仅1例患者发生吻合口漏（AL）。无治疗或手术相关死亡。
基于我们的研究结果，特瑞普利单抗联合多西他赛和顺铂作为一种新型新辅助治疗方案在局部晚期ESCC中安全有效。
