Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater
Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater
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DOI：
10.1200/jco.18.00149
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发表时间：
2019-03-01
影响因子：
45.3
通讯作者：
Brahmer, Julie R.
中科院分区：
文献类型：
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作者：
Reck, Martin;Rodriguez-Abreu, Delvys;Brahmer, Julie R.
在随机、开放标签、III期KEYNOTE-024研究中，与含铂化疗相比，pembrolizumab显著改善了既往未经治疗、程序性死亡配体1肿瘤比例评分≥ 50%且无EGFR/ALK畸变的晚期非小细胞肺癌（NSCLC）患者的无进展生存期和总生存期（OS）。我们报告了更新的OS和耐受性分析，包括分析调整潜在的偏差引入交叉化疗pembrolizum.Patients和MethodsPatients被随机分配到pembrolizum 200毫克每3周（长达2年）或研究者的选择铂为基础的化疗（4至6个周期）。分配至化疗组的患者在符合合格性标准后可交叉至pembrolizumab组。主要终点是无进展生存期; OS是重要的关键次要终点。交叉调整分析采用以下三种方法：简化两阶段的方法，秩保持结构故障的时间，和逆概率截尾weighting.ResultsThree百5例患者被随机分配（pembrolizumab，n = 154;化疗，n = 151）。在数据截止日期（2017年7月10日;中位随访时间为25.2个月），pembrolizumab组有73名患者死亡，化疗组有96名患者死亡。帕博利珠单抗组的中位OS为30.0个月（95% CI，18.3个月至未达到），化疗组为14.2个月（95% CI，9.8至19.0个月）（风险比，0.63; 95% CI，0.47至0.86）。82名分配接受化疗的患者在研究中交叉接受帕博利珠单抗治疗。当使用两阶段方法进行交叉校正时，帕博利珠单抗与化疗的OS风险比为0.49（95% CI，0.34 - 0.69）;使用等级保留结构失效时间和截尾加权逆概率的结果相似。治疗相关的3级至5级不良事件发生率较低与pembrolizumab化疗相比（31.2%v 53.3%，分别）。ConclusionWith long-term follow-up，一线pembrolizumab单药治疗继续表现出OS的好处化疗患者既往未经治疗，晚期NSCLC无EGFR/ALK畸变，尽管交叉从对照组pembrolizumab作为后续治疗。
PurposeIn the randomized, open-label, phase III KEYNOTE-024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in patients with previously untreated advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab.Patients and MethodsPatients were randomly assigned to pembrolizumab 200 mg every 3 weeks (for up to 2 years) or investigator's choice of platinum-based chemotherapy (four to six cycles). Patients assigned to chemotherapy could cross over to pembrolizumab upon meeting eligibility criteria. The primary end point was progression-free survival; OS was an important key secondary end point. Crossover adjustment analysis was done using the following three methods: simplified two-stage method, rank-preserving structural failure time, and inverse probability of censoring weighting.ResultsThree hundred five patients were randomly assigned (pembrolizumab, n = 154; chemotherapy, n = 151). At data cutoff (July 10, 2017; median follow-up, 25.2 months), 73 patients in the pembrolizumab arm and 96 in the chemotherapy arm had died. Median OS was 30.0 months (95% CI, 18.3 months to not reached) with pembrolizumab and 14.2 months (95% CI, 9.8 to 19.0 months) with chemotherapy (hazard ratio, 0.63; 95% CI, 0.47 to 0.86). Eighty-two patients assigned to chemotherapy crossed over on study to receive pembrolizumab. When adjusted for crossover using the two-stage method, the hazard ratio for OS for pembrolizumab versus chemotherapy was 0.49 (95% CI, 0.34 to 0.69); results using rank-preserving structural failure time and inverse probability of censoring weighting were similar. Treatment-related grade 3 to 5 adverse events were less frequent with pembrolizumab compared with chemotherapy (31.2% v 53.3%, respectively).ConclusionWith prolonged follow-up, first-line pembrolizumab monotherapy continues to demonstrate an OS benefit over chemotherapy in patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations, despite crossover from the control arm to pembrolizumab as subsequent therapy.