Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer.
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer.
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DOI：
10.1056/nejmoa1504627
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发表时间：
2015-07-09
期刊：
影响因子：
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通讯作者：
Spigel DR
中科院分区：
文献类型：
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作者：
Brahmer J;Reckamp KL;Baas P;Crinò L;Eberhardt WE;Poddubskaya E;Antonia S;Pluzanski A;Vokes EE;Holgado E;Waterhouse D;Ready N;Gainor J;Arén Frontera O;Havel L;Steins M;Garassino MC;Aerts JG;Domine M;Paz-Ares L;Reck M;Baudelet C;Harbison CT;Lestini B;Spigel DR
一线化疗期间或之后出现疾病进展的晚期鳞状细胞非小细胞肺癌（NSCLC）患者的治疗选择有限。这项随机、开放标签、国际、III期研究评估了nivolumab（一种全人源IgG 4程序性死亡1（PD-1）免疫检查点抑制剂抗体）与多西他赛相比在该患者人群中的疗效和安全性。我们将272名患者随机分配接受nivolumab，剂量为每公斤体重3 mg，每2周一次，或多西他赛，剂量为每平方米体表面积75 mg，每3周一次。主要终点是总生存期。nivolumab组的中位总生存期为9.2个月（95%置信区间[CI]，7.3至13.3），多西他赛组为6.0个月（95% CI，5.1至7.3）。纳武利尤单抗组的死亡风险比多西他赛组低41%（风险比，0.59; 95%CI，0.44 - 0.79; P<0.001）。1年时，纳武利尤单抗组的总生存率为42%（95% CI，34至50），多西他赛组为24%（95% CI，17至31）。纳武利尤单抗的缓解率为20%，多西他赛为9%（P = 0.008）。nivolumab组的中位无进展生存期为3.5个月，多西他赛组为2.8个月（死亡或疾病进展的风险比为0.62; 95%CI为0.47至0.81; P<0.001）。PD-1配体（PD-L1）的表达既不是预后，也不能预测获益。纳武利尤单抗组7%的患者报告了3级或4级治疗相关不良事件，而多西他赛组为55%。在既往接受过治疗的晚期鳞状细胞NSCLC患者中，无论PD-L1表达水平如何，nivolumab的总生存期、缓解率和无进展生存期均显著优于多西他赛。（由百时美施贵宝公司资助; CheckMate 017 ClinicalTrials.gov编号，NCT 01642004。）
Patients with advanced squamous-cell non–small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint–inhibitor antibody, as compared with docetaxel in this patient population. We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The response rate was 20% with nivolumab versus 9% with docetaxel (P = 0.008). The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group as compared with 55% of those in the docetaxel group. Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017 ClinicalTrials.gov number, NCT01642004.)