Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC
Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC
复制标题
DOI：
10.1016/j.jtho.2020.01.017
复制
发表时间：
2020-05-01
影响因子：
20.4
通讯作者：
He, Jie
中科院分区：
文献类型：
--
作者：
Gao, Shugeng;Li, Ning;He, Jie
简介：程序性死亡受体-1（PD-1）抑制剂在NSCLC的一线治疗中显示出疗效;然而，PD-1抑制剂作为新辅助治疗的证据有限。这是一项1b期研究，以评估PD-1抑制剂在新辅助setting.Methods的安全性和结果：治疗初治的可切除的NSCLC患者（阶段IA-IIIB）接受两个周期的sintiliumab（200毫克，静脉注射，第1天的22）。在第29天至第43天之间进行手术。在基线和手术前进行正电子发射断层扫描-计算机断层扫描。主要终点是安全性。疗效终点包括主要病理学缓解率（MPR）和客观缓解率。结果：共入组40例患者，所有患者均接受2剂sintiliumab治疗，37例患者行根治性切除术。共有21例患者（52.5%）发生了新辅助治疗相关不良事件（TRAE）。4例患者（10.0%）发生3级或以上新辅助TRAE，1例患者发生5级TRAE。8例患者达到放射学部分缓解，客观缓解率为20.0%。37例患者中，15例（40.5%）获得MPR，其中6例（16.2%）原发性肿瘤病理完全缓解，3例（8.1%）淋巴结完全缓解。鳞状细胞NSCLC的缓解率上级腺癌（MPR：48.4% vs 0%）。sintilimab治疗后最大标准化摄取值的降低与病理缓解相关（p < 0.00001）。基线时间质细胞而非肿瘤细胞的程序性细胞死亡配体1表达与病理学消退相关（p = 0.0471）。结论：新辅助sintiliumab治疗NSCLC患者是可以耐受的，MPR率为40.5%。sintiliumab治疗后最大标准化摄取值的降低可能预测病理反应。(C)2020年国际肺癌研究协会。爱思唯尔公司出版
Introduction: Programmed death receptor-1 (PD-1) inhibitors have shown efficacy in first-line treatment of NSCLC; however, evidence of PD-1 inhibitor as neoadjuvant treatment is limited. This is a phase 1b study to evaluate the safety and outcome of PD-1 inhibitor in neoadjuvant setting.Methods: Treatment-naive patients with resectable NSCLC (stage IA-IIIB) received two cycles of sintilimab (200 mg, intravenously, day 1 out of 22). Operation was performed between day 29 and 43. Positron emission tomography-computed tomography scans were obtained at baseline and before the operation. The primary end point was safety. Efficacy end points included rate of major pathologic response (MPR) and objective response rate. Expression of programmed cell death ligand 1 was also evaluated (registration number: ChiCTR-OIC-17013726).Results: A total of 40 patients enrolled, all of whom received two doses of sintilimab and 37 underwent radical resection. A total of 21 patients (52.5%) experienced neoadjuvant treatment-related adverse events (TRAEs). Four patients (10.0%) experienced grade 3 or higher neoadjuvant TRAEs, and one patient had grade 5 TRAE. Eight patients achieved radiological partial response, resulting in an objective response rate of 20.0%. Among 37 patients, 15 (40.5%) achieved MPR, including six (16.2%) with a pathologic complete response in primary tumor and three (8.1%) in lymph nodes as well. Squamous cell NSCLC exhibited superior response compared with adenocarcinoma (MPR: 48.4% versus 0%). Decrease of maximum standardized uptake values after sintilimab treatment correlated with pathologic remission (p < 0.00001). Baseline programmed cell death ligand 1 expression of stromal cells instead of tumor cells was correlated with pathologic regression (p = 0.0471).Conclusions: Neoadjuvant sintilimab was tolerable for patients with NSCLC, and 40.5% MPR rate is encouraging. The decrease of maximum standardized uptake values after sintilimab might predict pathologic response. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc.