Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China.
J Thorac Oncol. 2019 May;14(5):867-875. doi: 10.1016/j.jtho.2019.01.006. Epub 2019 Jan 17.
Data on immuno-oncology agents in Chinese patients are limited despite a need for new therapies. We evaluated the efficacy and safety of nivolumab in a predominantly Chinese patient population with previously treated NSCLC.
CheckMate 078 was a randomized, open-label, phase III clinical trial in patients from China, Russia, and Singapore with squamous or nonsquamous NSCLC that had progressed during/after platinum-based doublet chemotherapy (ClinicalTrials.gov: NCT02613507). Patients with EGFR/ALK alterations were excluded. Patients (N = 504) were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m every 3 weeks), stratified by performance status, tumor histology, and tumor programmed death ligand 1 expression. The primary endpoint was overall survival (OS); secondary endpoints included objective response rate, progression-free survival, and safety.
OS was significantly improved with nivolumab (n = 338) versus docetaxel (n = 166); median OS (95% confidence interval): 12.0 (10.4-14.0) versus 9.6 (7.6-11.2) months, respectively; hazard ratio (97.7% confidence interval): 0.68 (0.52-0.90); p = 0.0006. Objective response rate was 17% with nivolumab versus 4% with docetaxel; median duration of response was not reached versus 5.3 months. Minimum follow-up was 8.8 months. The frequency of grade 3 or greater treatment-related adverse events was 10% with nivolumab and 48% with docetaxel.
This is the first phase III study in a predominantly Chinese population reporting results with a programmed death 1 inhibitor. In this population with previously treated advanced NSCLC, nivolumab improved OS versus docetaxel. Results were consistent with global CheckMate 017 and 057 studies.
尽管需要新的疗法，但中国患者的免疫肿瘤药物数据有限。我们评估了纳武利尤单抗在既往接受过治疗的非小细胞肺癌（NSCLC）的以中国患者为主的患者人群中的疗效和安全性。
CheckMate 078 是一项在中国、俄罗斯和新加坡进行的随机、开放标签、III 期临床试验，纳入了接受过铂类双联化疗期间/之后进展的鳞状或非鳞状 NSCLC 患者（ClinicalTrials.gov：NCT02613507）。排除有 EGFR/ALK 改变的患者。504 例患者按体能状态、肿瘤组织学和肿瘤程序性死亡配体 1 表达情况以 2:1 的比例随机分配至纳武利尤单抗（3 mg/kg，每 2 周一次）或多西他赛（75 mg/m，每 3 周一次）组。主要终点为总生存期（OS）；次要终点包括客观缓解率、无进展生存期和安全性。
纳武利尤单抗（n=338）与多西他赛（n=166）相比，OS 显著改善；中位 OS（95%置信区间）：12.0（10.4-14.0）与 9.6（7.6-11.2）个月，风险比（97.7%置信区间）：0.68（0.52-0.90）；p=0.0006。纳武利尤单抗的客观缓解率为 17%，多西他赛为 4%；中位缓解持续时间未达到与 5.3 个月。最小随访时间为 8.8 个月。纳武利尤单抗组 3 级或更高级别的治疗相关不良事件发生率为 10%，多西他赛组为 48%。
这是第一项在以中国患者为主的人群中开展的 III 期研究，报告了程序性死亡 1 抑制剂的研究结果。在既往接受过治疗的晚期 NSCLC 中国患者中，与多西他赛相比，纳武利尤单抗改善了 OS。结果与全球 CheckMate 017 和 057 研究一致。
