MET Testing and Treatment Sequencing After Disease Progression on First-Line Osimertinib in Patients With EGFR-Mutated Advanced NSCLC and Acquired MET Overexpression and/or Amplification: A Global Real-World Study

IF 3.9 3区医学 Q2 ONCOLOGY

Clinical lung cancer Pub Date : 2026-10-01 Epub Date: 2026-08-24 DOI:10.1016/j.cllc.2026.08.011

Julia Rotow, Umberto Malapelle, Daniel Cuadras, Núria Lara, Noelia Caro, Montserrat Roset, Montse Pedros, Yacob Pinchevsky, YongJin Kim

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引用次数: 0

Abstract

Background

Given the potential benefit of MET-tyrosine kinase inhibitors (TKIs) after progression on osimertinib in EGFR-mutated advanced NSCLC, evaluating real-world biomarker testing and treatment sequencing is important. We report findings from a global, direct-to-physician, survey-based chart review.

Patients and Methods

Physicians treating NSCLC were surveyed regarding rebiopsy and MET testing practices and awareness of MET overexpression and/or amplification (OverExp/Amp) cutoff levels. Biomarker testing, MET OverExp/Amp quantification and treatment sequencing were assessed in patients with EGFR-mutated advanced NSCLC with acquired MET OverExp/Amp after progression on first-line osimertinib, who received second-line treatment between January 2018 and December 2023 (data cutoff: April 8, 2025).

Results

Among 280 physicians, rebiopsy practices varied; the most commonly reported MET testing method was NGS (78%), followed by IHC (11%) and FISH (11%). Understanding of MET OverExp/Amp cutoff levels varied, with 35%-47% of physicians unaware of appropriate cutoffs. Among 367 patients (94% with MET Amp), MET alterations were mostly detected through tissue-based (58%) versus liquid-based tests (31%) or both (11%). MET alterations were detected using NGS (77%), then PCR (10%), IHC (10%), and FISH (4%). In 257 patients with MET cutoff data available, most MET Amp had gene copy numbers ≥6 (88%). MET-TKIs (29%) and EGFR-TKIs (24%) were the most common second-line treatments, followed by chemotherapy (20%). Of 193 patients with high MET levels, most received targeted treatments (MET-TKI 35%, EGFR-TKI 23%).

Conclusion

Rebiopsy practices and knowledge of MET OverExp/Amp cutoffs varied among physicians. IHC/FISH were underutilized; however, their use should be encouraged for optimal patient identification and treatment selection.

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egfr突变的晚期NSCLC和获得性MET过表达和/或扩增患者在一线奥西替尼治疗进展后的MET检测和治疗测序：一项全球现实世界研究

背景：考虑到在egfr突变的晚期NSCLC患者使用奥西替尼治疗进展后使用met -酪氨酸激酶抑制剂（TKIs）的潜在益处，评估真实世界的生物标志物检测和治疗测序是很重要的。我们报告的结果来自一项全球性的、直接面向医生的、基于调查的图表回顾。患者和方法：对治疗NSCLC的医生进行了关于再活检和MET检测实践以及MET过表达和/或扩增（OverExp/Amp）截止水平的认识的调查。在2018年1月至2023年12月期间（数据截止日期：2025年4月8日）接受一线奥西替尼治疗进展后获得性MET OverExp/Amp的egfr突变晚期NSCLC患者中，评估了生物标志物检测、MET OverExp/Amp定量和治疗测序。结果：在280名医生中，重新活检的做法各不相同；最常见的MET检测方法是NGS(78%)，其次是IHC（11%）和FISH（11%）。对MET过经验/Amp临界值的理解各不相同，35%-47%的医生不知道适当的临界值。在367名患者（94%患有MET Amp）中，MET改变主要通过组织检测（58%）而不是液体检测（31%）或两者同时检测（11%）。使用NGS检测MET改变（77%），然后是PCR(10%)，免疫组化（10%）和FISH（4%）。在257例有MET截止数据的患者中，大多数MET Amp的基因拷贝数≥6（88%）。MET-TKIs（29%）和EGFR-TKIs（24%）是最常见的二线治疗，其次是化疗（20%）。在193名高MET水平患者中，大多数接受了靶向治疗（MET- tki 35%, EGFR-TKI 23%）。结论：医生的复查实践和对MET过exp /Amp截止值的认识各不相同。IHC/FISH未得到充分利用；然而，他们的使用应该鼓励最佳的病人识别和治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical lung cancer 医学-肿瘤学

CiteScore

7.00

自引率

2.80%

发文量

159

审稿时长

24 days

期刊介绍： Clinical Lung Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lung cancer. Clinical Lung Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of lung cancer. The main emphasis is on recent scientific developments in all areas related to lung cancer. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.