Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1-Positive Advanced NSCLC
Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1-Positive Advanced NSCLC
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DOI：
10.1016/j.jtho.2021.05.001
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发表时间：
2021-10-01
影响因子：
20.4
通讯作者：
Baas, Paul
中科院分区：
文献类型：
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作者：
Herbst, Roy S.;Garon, Edward B.;Baas, Paul
简介：在Keynote-010研究中，与多西紫杉醇相比，培溴利珠单抗改善了患有程序性死亡配体1(PD-L1)的晚期非小细胞肺癌(NSCLC)患者的总存活率(OS)，肿瘤比例评分(TPS)和肿瘤比例评分(TPS)分别为50%和1%。我们报告了Keynote-010研究的5年疗效和安全性随访。方法：患者被随机分为培溴利珠单抗2 mg/kg或10 mg/kg每3周一次或多西紫杉醇75 mg/m(2)每3周一次，共35个周期(2年)。完成pembrolizumab治疗并随后复发的患者可以接受第二疗程的pembrolizumab，最长可达17个周期(1年)。结果：共1034例患者被随机分为两组(培溴利珠单抗691例，多西紫杉醇343例)。中位研究随访期为67.4个月(范围：60.0-77.9)。PD-L1 TPS>；=50%和PD-L1 TPS>；=1%的患者OS的危险比(95%可信区间)分别为0.55(0.44-0.69)和0.70(0.6-10.80)。在PD-L1 TPS&Gt；=50%和PD-L1 TPS&Gt；=1%的患者中，培溴利珠单抗和多西紫杉醇的5年OS率分别为25.0%和8.2%和15.6%和6.5%。在完成35个周期/2年的79例患者中，完成3年后的OS率为83.0%(与随机分组的5年相似)。共有21名患者接受了第二疗程的培溴利珠单抗治疗；11名(52.4%)在开始第二疗程后有客观反应，15名(71.4%)在数据截止时存活。探索性生物标记物分析显示，较高的组织肿瘤突变负荷(每个外显子组175个突变)与培溴利珠单抗的疗效改善有关。结论：培溴利珠单抗继续为PD-L1 TPS>；=50%和>；=1%的晚期非小细胞肺癌患者提供比多西紫杉醇更长期的益处。我们的发现证实了pembrolizumab是二线或更晚情况下的标准治疗。(C)爱思唯尔公司代表国际肺癌研究协会出版的《2021年》。
Introduction: In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in patients with previously treated, advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) >= 50% and >= 1%. We report 5-year efficacy and safety follow-up for the KEYNOTE-010 study.Methods: Patients were randomized to pembrolizumab 2 mg/kg or 10 mg/kg once every 3 weeks or docetaxel 75 mg/m(2) once every 3 weeks for up to 35 cycles (2 y). Patients who completed pembrolizumab treatment and subsequently had recurrence could receive second-course pembrolizumab for up to 17 cycles (1 y). Pembrolizumab doses were pooled in this analysis.Results: A total of 1034 patients were randomized (pembrolizumab, n = 691; docetaxel, n = 343). Median study follow-up was 67.4 months (range: 60.0-77.9). The hazard ratio (95% confidence interval) for OS was 0.55 (0.44-0.69) for patients with PD-L1 TPS >= 50% and 0.70 (0.6-10.80) with PD-L1 TPS >= 1%. The 5-year OS rates for pembrolizumab versus docetaxel were 25.0% versus 8.2% in patients with PD-L1 TPS >= 50% and 15.6% versus 6.5% with PD-L1 TPS >= 1%. Among 79 patients who completed 35 cycles/2 years of pembrolizumab, the OS rate 3 years after completion (similar to 5 y from randomization) was 83.0%. A total of 21 patients received second-course pembrolizumab; 11 (52.4%) had an objective response after starting the second course and 15 (71.4%) were alive at data cutoff. Exploratory biomarker analysis revealed that higher tissue tumor mutational burden (>= 175 mutations per exome) was associated with improved outcomes with pembrolizumab.Conclusions: Pembrolizumab continued to provide long-term benefit than docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS >= 50% and >= 1%. Our findings confirm pembrolizumab as a standard-of-care treatment in the second-line or later setting. (C) 2021 Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.