MET 扩增是 EGFR 突变非小细胞肺癌 (NSCLC) 中对 EGFR 抑制的常见耐药机制。多项试验显示 EGFR 和 MET 联合抑制 (EGFRi/METi) 取得了令人鼓舞的结果。然而，MET 扩增的定义不一致，通常包括多体性和真实扩增。这是一项针对疾病进展患者的 EGFR 抑制和 MET 拷贝数增益 (CNG) 的多中心、真实世界分析，定义为真实扩增 (MET 7号染色体着丝粒比率[MET-CEP7]≥2）或多体性（基因拷贝数≥5，MET-CEP7<2）。共纳入43例MET CNG患者，其中42例经FISH检测。 23 名、7 名和 14 名分别接受了 EGFRi/METi、METi 和 SoC。与 METi (29%, 4-71) 相比，EGFRi/METi 队列中的患者表现出更高的现实临床获益率 (定义为疾病稳定或更好) 82% (95% 置信区间 [CI], 60-95) ）和 SoC（50%，23-77）。 EGFRi/METi 组的实际中位无进展生存期更长，为 9.8 个月，而 METi 组为 4.3 个月（风险比 [HR]，0.19，95% CI，0.06-0.57），SoC 组为 3.7 个月（0.41，0.18-0.91） ）， 分别。总体生存率在数值上得到改善。治疗和 CNG 类型（扩增与多体性）的相互作用分析表明，差异完全由接受 EGFRi/METi 的 MET 扩增患者驱动（OS 的 HR，0.09、0.01-0.54）。在这项真实世界研究中，EGFRi/ METi 显示出优于 METi 和 SoC 的临床优势。未来的研究应重点关注 MET CNG 类型的差异影响，重点关注真正的 MET 放大作为反应的预测因子。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

MET amplification is a common resistance mechanism to EGFR inhibition in EGFR-mutant non-small cell lung cancer (NSCLC). Several trials showed encouraging results with combined EGFR and MET inhibition (EGFRi/METi). However, MET amplification has been inconsistently defined and frequently included both polysomy and true amplification.This is a multicenter, real-world analysis in patients with disease progression on EGFR inhibition and MET copy number gain (CNG), defined as either true amplification (MET to centromere of chromosome 7 ratio [MET-CEP7] ≥ 2) or polysomy (gene copy number ≥ 5, MET-CEP7 < 2).A total of 43 patients with MET CNG were included, 42 of whom were detected by FISH. Twenty-three, 7, and 14 received EGFRi/METi, METi, and SoC, respectively. Patients in the EGFRi/METi cohort exhibited a superior real-world clinical benefit rate, defined as stable disease or better, of 82% (95% confidence interval [CI], 60-95) compared to METi (29%, 4-71) and SoC (50%, 23-77). Median real-world progression-free survival was longer with EGFRi/METi with 9.8 vs. 4.3 months with METi (hazard ratio [HR], 0.19, 95% CI, 0.06-0.57) and 3.7 months with SoC (0.41, 0.18-0.91), respectively. Overall survival was numerically improved. Interaction analysis with treatment and type of CNG (amplification vs. polysomy) suggests that differences were exclusively driven by MET-amplified patients receiving EGFRi/METi (HR for OS, 0.09, 0.01-0.54).In this real-world study, EGFRi/METi showed clinical benefit over METi and SoC. Future studies should focus on the differential impact of the type of MET CNG with a focus on true MET amplification as predictor of response.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.