Duan Hongtao, Wang Tianhu, Luo Zhilin, Tong Liping, Dong Xiaoping, Zhang Yong, Afzal Muhammad Zubair, Correale Pierpaolo, Liu Honggang, Jiang Tao, Yan Xiaolong
Department of Thoracic Surgery, Tangdu Hospital, Air Force Military Medical University, Xi'an, China.
Department of Thoracic Surgery, Third Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Transl Lung Cancer Res. 2021 Feb;10(2):1020-1028. doi: 10.21037/tlcr-21-130.
Neoadjuvant therapy has significantly improved the 5-year overall survival (OS) of patients with resectable non-small cell lung cancer (NSCLC). The CheckMate 159 trial showed that neoadjuvant therapy with a single-drug programmed cell death protein 1 (PD-1) inhibitor (nivolumab) achieved major pathological response (MPR) and pathological complete response (pCR) in 45% and 15%of participants, respectively. We conducted an open-label single-arm study to evaluate the safety and efficacy of neoadjuvant PD-1 inhibitors in combination with chemotherapy in the treatment of resectable NSCLC.
This study was conducted in a total of 2 hospitals in the Chinese cities of Xi'an and Chongqing, and included eligible patients over 18 years of age with clinically staged IIA-IIIB NSCLC. All patients were scheduled to receive surgery within 4-6 weeks after neoadjuvant treatment (3-4 cycles) consisting of PD-1 inhibitors combined with a conventional chemotherapy regimen on day 1 of each 21-day cycle.
Twenty-three patients, 22 males, and 1 female with just one of them with no smoking habits) were diagnosed with NSCL C in a stage IIA (3 cases), IIB (3 cases), IIIA (8 cases), and IIIB (9cases) and no druggable driver mutations/translocations were addressed to receive neoadjuvant treatment between June 2018 and June 2020. The treatment was well tolerated with just 3 typical immune-related adverse events (hyperthyroidism, hyperglycemia, and rash) recorded. There was a partial response (PR) and stable disease (SD) in 17 (73.9%) and 6 (26.1%) patients, with an overall response rate (ORR) of 73.9% according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.1). Six of these patients resulted in pCR (30%) while ten of them showed a MPR (50%). Twenty patients underwent surgical resection after treatment, while further 3 refused surgery. Surgical procedure included video-assisted thoracoscopic resection (10 cases), Vinci Robot surgery (4 cases), and thoracotomy in 4 cases while there were secondary compliance-related thoracotomy in two cases. The pathology analysis revealed a R0 in 19 cases (19/20, 95%).
Our results suggest that the neoadjuvant approach with chemotherapy and PD-1 blocking mAbs is safe and active in patients with resectable NSCLC where is associated with a promising high ORR, MPR and pCR.
新辅助治疗显著提高了可切除非小细胞肺癌（NSCLC）患者的5年总生存率（OS）。CheckMate 159试验表明，单药程序性细胞死亡蛋白1（PD-1）抑制剂（纳武利尤单抗）新辅助治疗分别使45%和15%的参与者获得了主要病理缓解（MPR）和病理完全缓解（pCR）。我们开展了一项开放标签单臂研究，以评估新辅助PD-1抑制剂联合化疗治疗可切除NSCLC的安全性和疗效。
本研究在中国西安和重庆的2家医院进行，纳入年龄在18岁以上、临床分期为IIA-IIIB期NSCLC的合格患者。所有患者计划在新辅助治疗（3-4个周期）后4-6周内接受手术，新辅助治疗为每21天周期的第1天给予PD-1抑制剂联合传统化疗方案。
2018年6月至2020年6月期间，23例患者（22例男性，1例女性，仅1例无吸烟习惯）被诊断为NSCLC，分期为IIA期（3例）、IIB期（3例）、IIIA期（8例）和IIIB期（9例），且不存在可靶向治疗的驱动基因突变/易位，接受了新辅助治疗。治疗耐受性良好，仅记录到3例典型的免疫相关不良事件（甲状腺功能亢进、高血糖和皮疹）。17例（73.9%）患者出现部分缓解（PR），6例（26.1%）患者病情稳定（SD），根据实体瘤疗效评价标准（RECIST v.1.1），总缓解率（ORR）为73.9%。其中6例患者达到pCR（30%），10例患者达到MPR（50%）。20例患者治疗后接受了手术切除，另外3例拒绝手术。手术方式包括电视辅助胸腔镜切除术（10例）、达芬奇机器人手术（4例）和开胸手术4例，其中2例因依从性相关原因进行了二次开胸手术。病理分析显示切缘R0为19例（19/20，95%）。
我们的结果表明，化疗联合PD-1阻断单克隆抗体的新辅助治疗方法在可切除NSCLC患者中是安全有效的，具有较高的ORR、MPR和pCR。
