Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer
Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer
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DOI：
10.1200/jco.19.03136
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发表时间：
2020-05-10
影响因子：
45.3
通讯作者：
Garassino, Marina C.
中科院分区：
文献类型：
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作者：
Gadgeel, Shirish;Rodriguez-Abreu, Delvys;Garassino, Marina C.
在KEYNOTE-189研究中，与安慰剂+培美曲塞铂相比，一线治疗的培美曲塞铂联合帕博利珠单抗显著改善了转移性非鳞状非小细胞肺癌（NSCLC）患者的总生存期（OS）和无进展生存期（PFS），与肿瘤程序性死亡配体1（PD-L1）表达无关。我们报告了KEYNOTE-189（ClinicalTrials.gov：NCT 02578680）的最新分析。方法患者被随机分配（2：1）接受培美曲塞和铂加帕博利珠单抗（n = 410）或安慰剂（n = 206），每3周一次，共4个周期，然后培美曲塞维持加帕博利珠单抗或安慰剂，共35个周期。安慰剂联合治疗组中符合条件的疾病进展患者可以交叉接受帕博利珠单抗单药治疗。由中心审查根据RECIST（版本1.1）评估缓解。本次更新分析未分配α值。结果截至2018年9月21日（中位随访时间为23.1个月），更新后的中位（95% CI）OS为22.0（19.5 - 25.2）个月，帕博利珠单抗联合治疗组为10.7（8.7至13.6）个月（风险比[HR]，0.56; 95% CI，0.45至0.70]）。中位（95%CI）PFS分别为9.0（8.1至9.9）个月和4.9（4.7至5.5）个月（HR，0.48; 95%CI，0.40至0.58）。从随机化至接受下一线治疗时出现客观肿瘤进展或全因死亡（以先发生者为准）（无进展生存期-2; PFS-2）的中位（95% CI）时间分别为17.0（15.1至19.4）个月和9.0（7.6至10.4）个月（HR，0.49; 95% CI，0.40至0.59）。无论PD-L1表达或是否存在肝/脑转移，均观察到Pembrolizumab的OS和PFS获益。3-5级不良事件的发生率是相似的帕博利珠单抗组合（71.9%）和安慰剂组合（66.8%）group.CONCLUSION一线帕博利珠单抗加培美塞铂继续表现出显着改善OS和PFS在转移性非鳞状NSCLC，无论PD-L1表达或肝/脑转移，具有可控的安全性和耐受性。
PURPOSE In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous nonsmall-cell lung cancer (NSCLC), irrespective of tumor programmed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680).METHODS Patients were randomly assigned (2:1) to receive pemetrexed and platinum plus pembrolizumab (n = 410) or placebo (n = 206) every 3 weeks for 4 cycles, then pemetrexed maintenance plus pembrolizumab or placebo for up to a total of 35 cycles. Eligible patients with disease progression in the placebo-combination group could cross over to pembrolizumab monotherapy. Response was assessed per RECIST (version 1.1) by central review. No alpha was assigned to this updated analysis.RESULTS As of September 21, 2018 (median follow-up, 23.1 months), the updated median (95% CI) OS was 22.0 (19.5 to 25.2) months in the pembrolizumab-combination group versus 10.7 (8.7 to 13.6) months in the placebo-combination group (hazard ratio [HR], 0.56; 95% CI, 0.45 to 0.70]). Median (95% CI) PFS was 9.0 (8.1 to 9.9) months and 4.9 (4.7 to 5.5) months, respectively (HR, 0.48; 95% CI, 0.40 to 0.58). Median (95% CI) time from randomization to objective tumor progression on next-line treatment or death from any cause, whichever occurred first (progression-free-survival-2; PFS-2) was 17.0 (15.1 to 19.4) months and 9.0 (7.6 to 10.4) months, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). OS and PFS benefits with pembrolizumab were observed regardless of PD-L1 expression or presence of liver/brain metastases. Incidence of grade 3-5 adverse events was similar in the pembrolizumab-combination (71.9%) and placebo-combination (66.8%) groups.CONCLUSION First-line pembrolizumab plus pemetrexed-platinum continued to demonstrate substantially improved OS and PFS in metastatic nonsquamous NSCLC, regardless of PD-L1 expression or liver/brain metastases, with manageable safety and tolerability.