Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.
Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.
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DOI：
10.1056/nejmoa1507643
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发表时间：
2015-10-22
期刊：
影响因子：
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通讯作者：
Brahmer JR
中科院分区：
文献类型：
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作者：
Borghaei H;Paz-Ares L;Horn L;Spigel DR;Steins M;Ready NE;Chow LQ;Vokes EE;Felip E;Holgado E;Barlesi F;Kohlhäufl M;Arrieta O;Burgio MA;Fayette J;Lena H;Poddubskaya E;Gerber DE;Gettinger SN;Rudin CM;Rizvi N;Crinò L;Blumenschein GR Jr;Antonia SJ;Dorange C;Harbison CT;Graf Finckenstein F;Brahmer JR
一线化疗后疾病进展的非鳞状非小细胞肺癌（NSCLC）患者的选择有限。这项随机、开放标签、国际III期研究评估了纳武利尤单抗与多西他赛在铂双联化疗失败后的患者人群中的疗效和安全性。患者随机接受nivolumab 3 mg/kg，每2周一次或多西他赛75 mg/m2，每3周一次。主要终点是总生存期。与多西他赛相比，纳武利尤单抗改善了总生存期。nivolumab组（n=292）的中位总生存期为12.2个月（95%CI，9.7至15.0），多西他赛组（n= 290）为9.4个月（95%CI，8.1至10.7）（风险比，0.73; 96%CI，0.59至0.89; P=0.002）。纳武利尤单抗的1年总生存率为51%（95% CI，45至56），多西他赛为39%（95% CI，33至45）。仅总生存期可获得额外随访的更新疗效结果：纳武利尤单抗的18个月总生存率为39%（95% CI，34至45），多西他赛为23%（95% CI，19至28）。nivolumab的缓解率为19%，多西他赛为12%（P=0.02）。虽然无进展生存期不利于nivolumab（nivolumab为2.3个月，多西他赛为4.2个月），但nivolumab的1年无进展生存期（19%）高于多西他赛（8%）。在预定义的≥ 1%、≥ 5%和≥10%程序性死亡-1配体1（PD-L1）肿瘤膜表达水平下，纳武利尤单抗进一步改善了所有终点的疗效。10%的纳武利尤单抗和54%的紫杉醇治疗患者报告了3-5级治疗相关不良事件。与多西他赛相比，纳武利尤单抗表现出上级总生存期，PD-L1表达增强了铂类化疗失败后晚期非鳞状NSCLC患者的疗效。纳武单抗的安全性特征优于多西他赛。
Options for patients with non-squamous non-small cell lung cancer (NSCLC) whose disease progresses after first-line chemotherapy are limited. This randomized, open-label, international phase 3 study evaluated efficacy and safety of nivolumab versus docetaxel in this patient population after failure of platinum doublet chemotherapy. Patients were randomized to nivolumab 3 mg per kilogram every 2 weeks or docetaxel 75 mg per square meter every 3 weeks. The primary endpoint was overall survival. Nivolumab improved overall survival versus docetaxel. Median overall survival was 12.2 months (95% CI, 9.7 to 15.0) for nivolumab (n=292) and 9.4 months (95% CI, 8.1 to 10.7) for docetaxel (n=290) (hazard ratio, 0.73; 96% CI, 0.59 to 0.89; P=0.002). One-year overall survival rates were 51% (95% CI, 45 to 56) for nivolumab and 39% (95% CI, 33 to 45) for docetaxel. Updated efficacy results with additional follow up are available for overall survival only: 18-month overall survival rates were 39% (95% CI, 34 to 45) for nivolumab and 23% (95% CI, 19 to 28) for docetaxel. Response rates were 19% for nivolumab and 12% for docetaxel (P=0.02). Although progression-free survival did not favor nivolumab (2.3 months for nivolumab versus 4.2 months for docetaxel), 1-year progression-free survival was higher for nivolumab (19%) than docetaxel (8%). Nivolumab further improved efficacy across all endpoints at predefined ≥1%, ≥5%, and ≥10% programmed death-1 ligand 1 (PD-L1) tumor membrane expression levels. Grade 3–5 treatment-related adverse events were reported in 10% of nivolumab and 54% of docetaxel-treated patients. Compared to docetaxel, nivolumab demonstrated superior overall survival, with PD-L1 expression conferring enhanced efficacy in patients with advanced non-squamous NSCLC after failure of platinum-based chemotherapy. The safety profile of nivolumab was favorable versus docetaxel.