Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer
Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer
复制标题
DOI：
10.1056/nejmoa1709937
复制
发表时间：
2017-11-16
影响因子：
158.5
通讯作者：
Ozguroglu, M.
中科院分区：
文献类型：
--
作者：
Antonia, S. J.;Villegas, A.;Ozguroglu, M.
背景：大多数局部晚期、不可切除的非小细胞肺癌（NSCLC）患者，尽管接受了明确的放化疗（化疗加同步放疗），但仍有疾病进展。这项3期研究比较了抗程序性死亡配体1抗体durvalumab作为巩固治疗与安慰剂在2个或以上铂基放化疗周期后无疾病进展的III期NSCLC患者中的应用。方法：我们以2:1的比例随机分配患者，每2周接受durvalumab（静脉注射剂量为每公斤体重10mg）或安慰剂，持续12个月。研究药物在患者接受放化疗后1至42天给予。主要终点是无进展生存期（通过盲法独立中心回顾评估）和总生存期（中期分析未计划）。次要终点包括12个月和18个月的无进展生存率、客观缓解率、缓解持续时间、死亡或远处转移时间以及安全性。在接受随机分组的713例患者中，709例接受了巩固治疗（473例接受杜伐单抗治疗，236例接受安慰剂治疗）。随机化后，durvalumab组的中位无进展生存期为16.8个月（95%可信区间[CI]， 13.0至18.1），安慰剂组为5.6个月（95% CI， 4.6至7.8）(疾病进展或死亡的分层风险比，0.52;95% CI， 0.42至0.65；P
BACKGROUNDMost patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy.METHODSWe randomly assigned patients, in a 2: 1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy. The coprimary end points were progression-free survival (as assessed by means of blinded independent central review) and overall survival (unplanned for the interim analysis). Secondary end points included 12-month and 18-month progression-free survival rates, the objective response rate, the duration of response, the time to death or distant metastasis, and safety.RESULTSOf 713 patients who underwent randomization, 709 received consolidation therapy (473 received durvalumab and 236 received placebo). The median progression-free survival from randomization was 16.8 months (95% confidence interval [CI], 13.0 to 18.1) with durvalumab versus 5.6 months (95% CI, 4.6 to 7.8) with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42 to 0.65; P