Shen Dijian, Chen Qixun, Wu Jie, Li Jianqiang, Tao Kaiyi, Jiang Youhua
Department of Thoracic surgery, Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
Institute of Cancer and Basic Medicine (IBMC), the Chinese Academy of Science, Hangzhou, China.
J Gastrointest Oncol. 2021 Feb;12(1):1-10. doi: 10.21037/jgo-20-599.
Neoadjuvant therapy followed by esophagectomy has been recognized as an effective treatment for locally advanced esophageal cancer, though still has a dismal prognosis. Antibodies against programmed death 1 (PD-1) protein improve survival in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) compared with chemotherapy in second-line therapy. However, neoadjuvant PD-1 inhibitor combined with chemotherapy has not been tested in locally advanced ESCC. We conducted this study to evaluate the efficacy and safety of pd-1 inhibitor in neoadjuvant chemotherapy.
In this study, we administered 28 adults with untreated, surgically resectable locally advanced ESCC. PD-1 inhibitor with chemotherapy [albumin paclitaxel 100 mg/m on days 1 and 8 + carboplatin with an area under the curve (AUC) of 5 on day 1] were administered every 3 weeks intravenously, and surgery was performed approximately 3-5 weeks after the second dose. The primary purpose of the study was to evaluate the feasibility and safety of this regimen.
In all, 28 locally advanced ESCC patients were enrolled, 27 patients received surgery, 9 (33.3%) patients' postoperative pathological specimens suggested pCR, and 11 (40.7%) patients' primary tumor suggested complete response. Neoadjuvant PD-1 inhibitor with chemotherapy had an acceptable side-effect profile, 26 patients' tumors were completely resected (96.3% were R0). According to the RESIST v.1.1, the response in all 27 patients was evaluated by a computed tomography (CT) scan before surgery, showing 12 patients with complete response (CR), 12 with partial response (PR), and 3 with stable disease (SD). For surgical procedures, 15 (55.6%) patients underwent minimal invasive surgery, 4 (14.8%) underwent right transthoracic open esophagectomy, and 8 (29.6%) underwent hybrid approaches.
The novel treatment of PD-1 inhibitor with chemotherapy in the neoadjuvant setting for locally advanced ESCC produced satisfactory outcomes: an unprecedentedly high pCR rate for neoadjuvant chemotherapy, a high R0 resection rate, and a low-toxicity profile were achieved. The long-term efficiency of this novel treatment and the validity of the present findings should be confirmed with longer follow-up and prospective comparative trials.
新辅助治疗后行食管切除术已被公认为是局部晚期食管癌的有效治疗方法，但其预后仍然不佳。与二线治疗中的化疗相比，抗程序性死亡蛋白1（PD-1）抗体可提高晚期或转移性食管鳞状细胞癌（ESCC）患者的生存率。然而，新辅助PD-1抑制剂联合化疗尚未在局部晚期ESCC中进行过测试。我们开展这项研究以评估PD-1抑制剂在新辅助化疗中的疗效和安全性。
在本研究中，我们纳入了28例未经治疗、可手术切除的局部晚期ESCC成年患者。每3周静脉给予1次PD-1抑制剂联合化疗[第1天和第8天给予白蛋白紫杉醇100mg/m² + 第1天给予曲线下面积（AUC）为5的卡铂]，在第2剂给药后约3 - 5周进行手术。本研究的主要目的是评估该方案的可行性和安全性。
总共纳入了28例局部晚期ESCC患者，27例患者接受了手术，9例（33.3%）患者的术后病理标本提示达到病理完全缓解（pCR），11例（40.7%）患者的原发肿瘤提示完全缓解。新辅助PD-1抑制剂联合化疗具有可接受的副作用，26例患者的肿瘤被完整切除（96.3%为R0切除）。根据RECIST v.协议1.1，在术前通过计算机断层扫描（CT）对所有27例患者的反应进行评估，显示12例患者完全缓解（CR），12例部分缓解（PR），3例疾病稳定（SD）。对于手术方式，15例（55.6%）患者接受了微创手术，4例（14.8%）接受了右胸开放式食管切除术，8例（29.6%）接受了混合手术方式。
在局部晚期ESCC的新辅助治疗中，PD-1抑制剂联合化疗的新治疗方法产生了令人满意的结果：新辅助化疗实现了前所未有的高pCR率、高R0切除率和低毒性。这种新治疗方法的长期疗效以及本研究结果的有效性应通过更长时间的随访和前瞻性对照试验来证实。
