Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC
Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC
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DOI：
10.1056/nejmoa1809697
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发表时间：
2018-12-13
影响因子：
158.5
通讯作者：
Ozguroglu, M.
中科院分区：
文献类型：
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作者：
Antonia, S. J.;Villegas, A.;Ozguroglu, M.
背景3期试验早些时候的分析表明，与安慰剂相比，在同时接受放化疗后没有疾病进展的III期不可切除非小细胞肺癌(NSCLC)患者中，Durvalumab显著延长了无进展生存期。在这里，我们报告了总存活率的第二个主要终点的结果。方法：我们按2：1的比例随机分配患者，按每公斤体重10毫克的剂量静脉注射杜伐单抗，或每两周服用一次安慰剂，最长持续12个月。随机分组发生在患者接受放化疗后1至42天，并根据年龄、性别和吸烟史进行分层。主要终点是无进展生存率(通过盲法独立的中央审查进行评估)和总体生存率。次要终点包括死亡或远处转移的时间、二次进展的时间和安全性。结果在713名接受随机分组的患者中，709名接受了指定的干预(473名患者接受了度伐卢单抗治疗，236名接受了安慰剂治疗)。截至2018年3月22日，中位随访时间为25.2个月。与安慰剂组的55.6%(95%可信区间，48.9~61.8)相比，杜伐单抗组的24个月总生存率为66.3%(95%可信区间，61.7%~70.4%)(双侧P=0.005)。与安慰剂相比，杜伐单抗显著延长了总生存期(死亡的分层风险比为0.68；99.73%可信区间为0.47%至0.997；P=0.0025)。关于无进展存活率的最新分析与以前报道的相似，杜伐单抗组的中位持续时间为17.2个月，安慰剂组为5.6个月(疾病进展或死亡的分层风险比，0.51；95%可信区间，0.41至0.63)。中位死亡或远处转移时间在杜伐单抗组为28.3个月，在安慰剂组为16.2个月(分层危险比，0.53；95%CI，0.41至0.68)。有30.5%的患者和26.1%的安慰剂组患者有3级或4级的任何原因的不良事件，分别有15.4%和9.8%的患者因不良事件而终止试验方案。结论：与安慰剂相比，单抗治疗的总生存期显著延长。没有发现新的安全信号。
BACKGROUNDAn earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival.METHODSWe randomly assigned patients, in a 2: 1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age, sex, and smoking history. The primary end points were progression-free survival (as assessed by blinded independent central review) and overall survival. Secondary end points included the time to death or distant metastasis, the time to second progression, and safety.RESULTSOf the 713 patients who underwent randomization, 709 received the assigned intervention (473 patients received durvalumab and 236 received placebo). As of March 22, 2018, the median follow-up was 25.2 months. The 24-month overall survival rate was 66.3% (95% confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two-sided P = 0.005). Durvalumab significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P = 0.0025). Updated analyses regarding progression-free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group had grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients, respectively, discontinued the trial regimen because of adverse events.CONCLUSIONSDurvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified.