| 关业兰,胡红林,金 莹,等.帕博利珠单抗联合培美曲塞和卡铂对比培美曲塞和卡铂一线治疗晚期、非鳞状非小细胞肺癌：Ⅱ期、随机、开放研究KEYNOTE-021G队列研究及长期随访数据解读[J].肿瘤学杂志,2022,28(9):786-796. |
| 帕博利珠单抗联合培美曲塞和卡铂对比培美曲塞和卡铂一线治疗晚期、非鳞状非小细胞肺癌：Ⅱ期、随机、开放研究KEYNOTE-021G队列研究及长期随访数据解读 |
| Pembrolizumab in Combination with Pemetrexed and Carboplatin Versus Pemetrexed Plus Carboplatin for the First-line Treatment of Advanced， Non-squamous NSCLC： Interpretation of Data from the Phase Ⅱ， Randomized， Open Study KEYNOTE-021G Cohort Study and Long-term Follow-up |
| 投稿时间：2022-08-11 |
| DOI：10.11735/j.issn.1671-170X.2022.09.B014 |
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| 中文关键词: 帕博利珠单抗 培美曲塞 卡铂 客观缓解率 不良事件 |
| 英文关键词:pembrolizumab pemetrexed carboplatin objective response rate adverse events |
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| 中文摘要: |
| 摘 要：KEYNOTE-021研究是一项随机、开放标签、多队列研究，其Ⅱ期研究G队列比较了培美曲塞和卡铂联合及不联合帕博利珠单抗在晚期、非鳞状非小细胞肺癌（non-small lung cancer，NSCLC）中作为一线治疗策略的疗效和安全性。主要研究终点是客观缓解率（objective response rate，ORR），次要研究终点为中位无进展生存期（progression-free survival，PFS），根据程序性死亡配体-1（programmed death ligand-1，PD-L1）肿瘤细胞阳性比例分数（tumor cell proportion score，TPS）＜1%、1%~49%和≥50%进行分层。结果显示，在ITT人群中，ORR在免疫联合化疗组和单纯化疗组分别为55%（33/60）和29%（18/63），估计治疗差异为26%（95% CI：9%~42%，P=0.001 6）；亚组分析显示，在PD-L1＜1%、1%~49%和≥50%患者中，ORR分别为57%（12/21）、26%（5/19）和80%（16/20）。次要研究终点中位PFS在免疫联合化疗组和单纯化疗组分别为13.0个月和8.9个月（HR=0.53，P=0.01）。两组3~4级不良反应发生率相似，免疫联合化疗组和单纯化疗组为39%（23/59）和26%（16/62）。更新的3年生存率显示，免疫联合化疗组和单纯化疗组分别为 50%和37%，ORR分别为58%和33%。在PD-L1＜1%和PD-L1≥1%的亚组中，免疫联合化疗组和单纯化疗组ORR分别为67%和17%，54%和43%。因此，不论PD-L1表达状态，免疫联合化疗均能显著性延长晚期NSCLC患者的生存期。此外，12例完成35个周期（2年）患者的估计3年肿瘤持续缓解时间均为100%。基于此项研究，2017年5月美国食品和药品管理局（FDA）加速批准了帕博利珠单抗联合培美曲塞和卡铂用于未经治疗的驱动基因阴性的晚期非鳞状NSCLC的一线治疗，并为后续的KEYNOTE-189扩大样本Ⅲ期研究奠定了基础。 |
| 英文摘要: |
| Abstract： The KEYNOTE-021 study is a randomized， open-label， multi-cohort study with a phase Ⅱ study G cohort comparing the efficacy and safety of pemetrexed and carboplatin in combination with and without pembrolizumab as a first-line treatment strategy in advanced， non-squamous non-small cell lung cancer(NSCLC). The primary study endpoint was the objective response rate(ORR) and the secondary study endpoint was the median progression-free survival(PFS). Patients were stratified based on the programmed death ligand-1(PD-L1) tumor cell proportion score(TPS) of <1%， 1%~49% and ≥50%. Results showed that in the ITT population， ORR was 55%(33/60) and 29%(18/63) in the immune combination chemotherapy and chemotherapy alone groups， respectively， with an estimated treatment difference of 26%(95% CI： 9%~42%， P=0.001 6)， subgroup analysis showed that in the PD-L1<1%， 1%~ 49% and ≥50%， the ORR was 57%(12/21)， 26%(5/19) and 80%(16/20). The median PFS for the secondary study endpoint was 13.0 and 8.9 months in the pembrolizumab combination chemotherapy and chemotherapy alone groups， respectively(HR=0.53， P=0.01). And the incidence of grade 3~4 adverse events was similar in both treatment groups， with 39%(23/59) vs 26%(16/62) in the combination therapy group vs chemotherapy alone group. Updated 3-years survival rates showed 50% and 37% in the pembrolizumab combination chemotherapy group versus chemotherapy alone group， with ORR of 58% vs 33%， respectively. In the PD-L1 <1% and ≥1% subgroups， the ORR was 67% vs 17% and 54% vs 43% for pembrolizumab combination chemotherapy versus chemotherapy alone， respectively. Therefore， pembrolizumab combination chemotherapy significantly prolonged the survival of patients with advanced NSCLC regardless of PD-L1 expression status. In addition， all 12 patients who completed 35 cycles(2 years) of treatment had an estimated 3-years duration of overall response of 100%. Based on this study， the US Food and Drug Administration(FDA) granted accelerated approval for pembrolizumab in combination with pemetrexed and carboplatin for the first-line treatment of untreated driver gene-negative advanced non-squamous NSCLC in May 2017 and set the stage for the subsequent KEYNOTE-189 expanded sample phase Ⅲ study. |
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