SCI

23 September 2024

Phase III KEYNOTE-789 Study of Pemetrexed and Platinum With or Without Pembrolizumab for Tyrosine Kinase Inhibitor‒Resistant, EGFR–Mutant, Metastatic Nonsquamous Non–Small Cell Lung Cancer

(Journal of Clinical Oncology, IF: 42.1)

  • James Chih-Hsin Yang; Dae Ho Lee,; Jong-Seok Lee; Yun Fan; Filippo de Marinis; Eiji Iwama; Takako Inoue; Jer ́onimo Rodr ́ıguez-Cid,; Li Zhang; Cheng-Ta Yang; Emmanuel de la Mora Jimenez; Jianying Zhou; Maurice P ́erol; Ki Hyeong Lee; David Vicente; Eiki Ichihara; Gregory J. Riely; Yiwen Luo; Diana Chirovsky; M. Catherine Pietanza; Niyati Bhagwati; and Shun Lu, MD

  • CORRESPONDENCE TO: chihyang@ntu.edu.tw

PURPOSE 目的

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR-mutant, metastatic non–small cell lung cancer (NSCLC); however, most patients experience disease progression. We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum–based chemotherapy with or without pembrolizumab for TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837).

表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）是治疗EGFR突变、转移性非小细胞肺癌（NSCLC）的标准一线疗法；然而，大多数患者都会经历疾病进展。我们报告了一项随机、双盲、III期KEYNOTE-789研究的结果，该研究对培美曲塞和铂类化疗联合或不联合帕博利珠单抗治疗TKI耐药、EGFR突变、转移性非鳞状非小细胞肺癌进行了探究（ClinicalTrials.gov标识符：NCT03515837）。

 

METHODS 方法

Adults with pathologically confirmed stage IV nonsquamous NSCLC, documented DEL19 or L858R EGFR mutation, and progression after EGFR-TKI treatment were randomly assigned 1:1 to 35 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus four cycles of pemetrexed and carboplatin or cisplatin once every 3 weeks and then maintenance pemetrexed. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Final PFS testing was completed at the second interim analysis (IA2; data cutoff, December 3, 2021); OS was tested at final analysis (FA; data cutoff, January17,2023). Efficacy boundaries were one-sided P = .0117 for PFS and OS.

将经病理证实为IV期非鳞状非小细胞肺癌、记录在案的DEL19或L858R EGFR突变以及EGFR-TKI治疗后进展的成年人随机1:1分配至每3周一次35个周期的培美曲单抗200mg或安慰剂组，加上每3周一次4个周期的培美曲塞和卡铂或顺铂，然后维持培美曲塞。双主要终点是无进展生存期（PFS）和总生存期（OS）。最终的PFS分析在第二次中期分析时完成（IA2；数据截止日期，2021年12月3日）；OS在最终分析时进行了测试（FA；数据截止日期，2023年1月17日）。PFS和OS的疗效边界为单侧P = 0.0117。

 

RESULTS 结果

Four hundred ninety-two patients were randomly assigned to pembrolizumab plus chemotherapy (n = 245) or placebo plus chemotherapy (n = 247). At IA2, the median PFS was 5.6 months for pembrolizumab plus chemotherapy versus 5.5 months for placebo plus chemotherapy (hazard ratio [HR], 0.80[95% CI, 0.65 to 0.97]; P = .0122). At FA, the median OS was 15.9 versus 14.7 months, respectively (HR,0.84[95%CI, 0.69 to 1.02]; P = .0362). Grade ≥ 3 treatment-related adverse events occurred in 43.7% of pembrolizumab plus chemotherapy recipients versus 38.6% of placebo plus chemotherapy recipients.

492名患者被随机分配到帕博利珠单抗加化疗（n = 245）或安慰剂加化疗（n = 247）组。在IA2时，帕博利珠单抗联合化疗组的中位无进展生存期为5.6个月，而安慰剂联合化疗组的中位无进展生存期为5.5个月（风险比[HR]，0.80[95%CI，0.65至0.97]；P=0.0122）。FA时，中位OS分别为15.9个月和14.7个月（HR，0.84[95%CI，0.69至1.02]；P=0.0362）。43.7%的帕博利珠单抗联合化疗受试者发生了≥3级治疗相关不良事件，而38.6%的安慰剂联合化疗受试者发生了≥3级治疗相关不良事件。

 

CONCLUSION 结论

Addition of pembrolizumab to chemotherapy in patients with TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS or OS versus placebo plus chemotherapy in KEYNOTE-789.

在KEYNOTE-789中，与安慰剂加化疗相比，在TKI耐药、EGFR突变、转移性非鳞状非小细胞肺癌患者的化疗中加入帕博利珠单抗并没有显著延长PFS或OS。