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Abstract：
In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data.
PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis.
At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS ≥1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)].
Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples.
ClinicalTrials.gov: NCT01905657.
PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis.
At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS ≥1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)].
Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples.
ClinicalTrials.gov: NCT01905657.
摘要：
在KEYNOTE-010中，派姆单抗与多西他赛相比可改善程序性死亡-1蛋白（PD）-L1阳性晚期非小细胞肺癌（NSCLC）患者的总生存期（OS）。预先指定的探索性分析使用最近更新的生存数据，比较了基于存档和新收集的肿瘤样本中PD-L1表达的患者的预后。
在存档或新收集的肿瘤样品中通过免疫组织化学(22C3抗体)集中评估PD-L1。患者接受派姆单抗2或10mg/kgQ3W或多西他赛75mg/m2Q3W，持续24个月或直至进展/无法耐受的毒性/其他原因。每9周通过RECISTv1.1评估反应，每2个月生存一次。主要终点为肿瘤比例评分（TPS）≥50%和≥1%的OS和无进展生存期（PFS）；本分析中合并了派博利珠单抗剂量。
截止日期为2017年3月24日，中位随访时间为31个月（范围23-41），代表主要分析的额外随访18个月。Pembrolizumab与多西他赛相比，在以前接受过治疗的患者中继续改善OS，PD-L1表达的晚期NSCLC；风险比（HR）为0.66[95％置信区间（CI）：0.57，0.77]。在分析的1033名患者中，455（44％）基于档案样本和578（56％）基于新收集的肿瘤样本。大约40%的档案样本和45%的新收集的肿瘤样本为PD-L1TPS≥50%。TPS≥50%时,档案和新收集样本的OSHR分别为0.64(95%CI：0.45，0.91)和0.40(95%CI：0.28，0.56)，分别。在TPS≥1%的患者中，档案样本和新收集样本的OSHR分别为0.74（95%CI：0.59，0.93）和0.59（95%CI：0.48，0.73），分别。TPS≥50%时，档案[0.63(95%CI:0.45,0.89)]和新收集的样本[0.53(95%CI:0.38,0.72)]的PFSHR相似。在TPS≥1%的患者中，档案[0.82(95%CI:0.66,1.02)]和新收集的样本[0.83(95%CI:0.68,1.02)]的PFSHR相似。
与多西他赛相比，Pembrolizumab在治疗人群和新收集和存档样本的患者亚组中继续改善OS。
ClinicalTrials.gov：NCT01905657。
在存档或新收集的肿瘤样品中通过免疫组织化学(22C3抗体)集中评估PD-L1。患者接受派姆单抗2或10mg/kgQ3W或多西他赛75mg/m2Q3W，持续24个月或直至进展/无法耐受的毒性/其他原因。每9周通过RECISTv1.1评估反应，每2个月生存一次。主要终点为肿瘤比例评分（TPS）≥50%和≥1%的OS和无进展生存期（PFS）；本分析中合并了派博利珠单抗剂量。
截止日期为2017年3月24日，中位随访时间为31个月（范围23-41），代表主要分析的额外随访18个月。Pembrolizumab与多西他赛相比，在以前接受过治疗的患者中继续改善OS，PD-L1表达的晚期NSCLC；风险比（HR）为0.66[95％置信区间（CI）：0.57，0.77]。在分析的1033名患者中，455（44％）基于档案样本和578（56％）基于新收集的肿瘤样本。大约40%的档案样本和45%的新收集的肿瘤样本为PD-L1TPS≥50%。TPS≥50%时,档案和新收集样本的OSHR分别为0.64(95%CI：0.45，0.91)和0.40(95%CI：0.28，0.56)，分别。在TPS≥1%的患者中，档案样本和新收集样本的OSHR分别为0.74（95%CI：0.59，0.93）和0.59（95%CI：0.48，0.73），分别。TPS≥50%时，档案[0.63(95%CI:0.45,0.89)]和新收集的样本[0.53(95%CI:0.38,0.72)]的PFSHR相似。在TPS≥1%的患者中，档案[0.82(95%CI:0.66,1.02)]和新收集的样本[0.83(95%CI:0.68,1.02)]的PFSHR相似。
与多西他赛相比，Pembrolizumab在治疗人群和新收集和存档样本的患者亚组中继续改善OS。
ClinicalTrials.gov：NCT01905657。
