Pembrolizumab联合培美曲塞和铂治疗非鳞状非小细胞肺癌癌症：Ⅲ期KEYNOTE-189研究的5年结果

SCI 13 March 2023

Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non–Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study

（Journal of Clinical Oncology；IF: 50.717）

CORRESPONDENCE TO: mgarassino@medicine.bsd. uchicago.edu. 

Marina C. Garassino, MD1,2; Shirish Gadgeel, MD3; Giovanna Speranza, MD, MSc4; Enriqueta Felip, MD, PhD5; Emilio Esteban, MD6; Manuel Do ́mine, MD7; Maximilian J. Hochmair, MD8; Steven F. Powell, MD9; Helge G. Bischoff, MD10; Nir Peled, MD11;

Francesco Grossi, MD12; Ross R. Jennens, MBBS13; Martin Reck, MD, PhD14; Rina Hui, MBBS, PhD15; Edward B. Garon, MD16; Takayasu Kurata, MD17; Jhanelle E. Gray, MD18; Paul Schwarzenberger, MD19; Erin Jensen, MS19; M. Catherine Pietanza, MD19; and Delvys Rodr ́ıguez-Abreu, MD, PhD20 

We present 5-year outcomes from the phase 3 KEYNOTE-189 study (ClinicalTrials.gov identifier: NCT02578680). Eligible patients with previously untreated metastatic nonsquamous non–small-cell lung cancer without EGFR/ALK alterations were randomly assigned 2:1 to pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles with pemetrexed and investigator’s choice of carboplatin/cisplatin for four cycles, followed by maintenance pemetrexed until disease progression or unacceptable toxicity. Primary end points were overall survival (OS) and progression-free survival (PFS). Among 616 randomly assigned patients (n=410, pembrolizumab plus pemetrexed-platinum; n=206, placebo plus pemetrexed-platinum), median time from random assignment to data cutoff (March 8, 2022) was 64.6 (range, 60.1-72.4) months. Hazard ratio (95% CI) for OS was 0.60 (0.50 to 0.72) and PFS was 0.50 (0.42 to 0.60) for pembrolizumab plus platinum- pemetrexed versus placebo plus platinum-pemetrexed. 5-year OS rates were 19.4% versus 11.3%. Toxicity was manageable. Among 57 patients who completed 35 cycles of pembrolizumab, objective response rate was 86.0% and 3-year OS rate after completing 35 cycles (approximately 5 years after random assignment) was 71.9%. Pembrolizumab plus pemetrexed-platinum maintained OS and PFS benefits versus placebo plus pemetrexed-platinum, regardless of programmed cell death ligand-1 expression. These data continue to support pembrolizumab plus pemetrexed-platinum as a standard of care in previously untreated metastatic non–small-cell lung cancer without EGFR/ALK alterations. 

本文介绍了Ⅲ期KEYNOTE-189研究的5年结果。符合条件的先前未经治疗的且EGFR/ALK无改变的转移性非鳞癌非小细胞肺癌的患者，随机按2:1分组，每3周服用一次200 mg pembrolizumab或安慰剂，最多35个周期，使用培美曲塞和研究者选择卡铂或顺铂，共四个周期，然后维持培美曲塞，直到疾病进展或不可接受的毒性。主要终点是总生存率（OS）和无进展生存率（PFS）。在616名随机分配的患者中（n=410，pembrolizumab加培美曲塞铂；n=206，安慰剂加培美曲塞铂），从随机分配到数据截止（2022年3月8日）的中位时间为64.6（60.1-72.4）个月。与安慰剂加培美曲塞铂相比，pembrolizumab加培美曲塞铂的OS风险比（95%CI）为0.60（0.50至0.72），PFS为0.50（0.42至0.60）。5年OS率为19.4%对11.3%。毒性可控。在57名完成了35个周期pembrolizumab治疗的患者中，客观有效率为86.0%，完成35个周期（随机分配后约5年）后的3年OS率为71.9%。与安慰剂加培美曲塞铂相比，pembrolizumab加培美曲塞铂对OS和PFS有益，而不考虑程序性细胞死亡配体-1的表达。这些数据继续支持pembrolizumab联合培美曲塞铂作为治疗未经治疗且无EGFR/ALK改变的转移性非鳞癌非小细胞肺癌的标准。

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