Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer
Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer
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DOI：
10.1056/nejmoa1801005
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发表时间：
2018-05-31
影响因子：
158.5
通讯作者：
Garassino, M. C.
中科院分区：
文献类型：
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作者：
Gandhi, L.;Rodriguez-Abreu, D.;Garassino, M. C.
背景缺乏靶向突变的晚期非小细胞肺癌（NSCLC）的一线治疗是以铂为基础的化疗。在程序性死亡配体1（PD-L1）肿瘤比例评分为50%或更高的患者中，派姆单抗已取代细胞毒性化疗作为一线治疗选择。在2期试验中，与单独化疗相比，在化疗基础上加用帕博利珠单抗可显著提高缓解率和延长无进展生存期。（在一个2：1比率）616例既往未接受过转移性疾病治疗的无致敏EGFR或ALK突变的转移性非鳞状NSCLC患者接受培美曲塞和铂类药物加200 mg派姆单抗或安慰剂，每3周一次，共4个周期，随后是派姆单抗或安慰剂，共35个周期加培美曲塞维持治疗。安慰剂联合治疗组中证实疾病进展的患者允许交叉至帕博利珠单抗单药治疗。主要终点是总生存期和无进展生存期，由盲法、独立的中心放射学评估。随访中位时间为10.5个月后，12个月总生存率估计为69.2%。（95%置信区间[CI]，64.1 - 73.8），帕博利珠单抗联合治疗组与49.4%（95%CI，42.1至56.2）（死亡风险比，0.49; 95%CI，0.38至0.64; P< 0.001）。在评价的所有PD-L1类别中均观察到总生存期改善。帕博利珠单抗联合治疗组的中位无进展生存期为8.8个月（95% CI，7.6 - 9.2），安慰剂联合治疗组为4.9个月（95% CI，4.7 - 5.5）（疾病进展或死亡的风险比为0.52; 95% CI，0.43 - 0.64; P< 0.001）。在pembrolizumab联合治疗组和安慰剂联合治疗组中，分别有67.2%和65.8%的患者发生了3级或3级以上的不良事件。在培美曲塞和铂类药物的标准化疗中添加帕博利珠单抗可显著延长总生存期和进展-比单纯化疗的存活率高。
BACKGROUNDFirst-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial.METHODSIn this double-blind, phase 3 trial, we randomly assigned (in a 2: 1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo-combination group who had verified disease progression. The primary end points were overall survival and progression-free survival, as assessed by blinded, independent central radiologic review.RESULTSAfter a median follow-up of 10.5 months, the estimated rate of overall survival at 12 months was 69.2% (95% confidence interval [CI], 64.1 to 73.8) in the pembrolizumab-combination group versus 49.4% (95% CI, 42.1 to 56.2) in the placebocombination group (hazard ratio for death, 0.49; 95% CI, 0.38 to 0.64; P< 0.001). Improvement in overall survival was seen across all PD-L1 categories that were evaluated. Median progression-free survival was 8.8 months (95% CI, 7.6 to 9.2) in the pembrolizumab-combination group and 4.9 months (95% CI, 4.7 to 5.5) in the placebo-combination group (hazard ratio for disease progression or death, 0.52; 95% CI, 0.43 to 0.64; P< 0.001). Adverse events of grade 3 or higher occurred in 67.2% of the patients in the pembrolizumab-combination group and in 65.8% of those in the placebo-combination group.CONCLUSIONSIn patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.