Pemetrexed and platinum with or without pembrolizumab for tyrosine kinase inhibitor (TKI)-resistant, EGFR -mutant, metastatic nonsquamous NSCLC: Phase 3 KEYNOTE-789 study.

作者：James Chih‐Hsin Yang, Dae Ho Lee, Jong Seok Lee, Yun Fan, Filippo de Marinis, Isamu Okamoto, Takako Inoue, Jerónimo Rafael Rodríguez Cid, Zhang Li, Cheng‐Ta Yang, Emmanuel de la Mora Jimenez, Jianying Zhou, M. Pérol, Ki Hyeong Lee, David Vicente, Eiki Ichihara, Gregory J. Riely, Yiwen Luo, Niyati Bhagwati, Shun Lü · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.17_suppl.lba9000 · 被引用次数：94 · 研究领域：Lung Cancer Treatments and Mutations、Advanced Breast Cancer Therapies、Cancer Genomics and Diagnostics

LBA9000 Background: EGFR TKIs are standard 1L therapy for metastatic NSCLC with sensitizing EGFR mutations; however, most patients (pts) ultimately experience PD. We report the protocol-specified final analysis (FA) from the randomized, double-blind, phase 3 KEYNOTE-789 study of pemetrexed (pem) and platinum-based chemotherapy (chemo) with or without pembrolizumab (pembro) as subsequent therapy for pts with TKI-resistant, EGFR-mutant, metastatic nonsquamous NSCLC (NCT03515837). Methods: Adults with histologically or cytologically confirmed stage IV nonsquamous NSCLC, ECOG PS of 0 or 1, documented DEL19 or L858R EGFR mutation, and progression after EGFR TKI treatment were enrolled. Pts were randomized 1:1 to 35 cycles of pembro 200 mg Q3W or placebo (pbo) Q3W plus 4 cycles of pem and carboplatin or cisplatin Q3W followed by maintenance pem. Randomization was stratified by PD-L1 TPS (<50% vs ≥50%), prior osimertinib (yes vs no), and region (East Asia vs not East Asia). Dual primary endpoints were PFS per RECIST v1.1 by blinded independent central review (BICR) and OS. ORR and DOR per RECIST v1.1 by BICR and safety were secondary endpoints. Final PFS testing was completed at the second interim analysis (IA2; data cutoff, Dec 3, 2021); all other endpoints were assessed at FA (data cutoff, Jan 17, 2023). Efficacy boundaries based on actual observed events were 1-sided P = 0.0117 for PFS (IA2) and P = 0.0118 for OS (FA). Results: 492 pts were randomized to pembro + chemo (n = 24...