Clinical significance of EGFR amplification in patients with EGFR -mutated metastatic non–small cell lung cancer receiving first-line osimertinib.

作者：Alessandro Di Federico, Federica Pecci, Mark Jeng, M. Peroni, Daniele Marinelli, Alessandro Leonetti, Francesco Mantuano, Roberta Minari, Stefano Scalera, Laura Cipriani, Marcello Maugeri‐Saccà, Nicola Calonaci, Giulio Caravagna, Biagio Ricciuti, Mark M. Awad, Federico Cappuzzo, M Tiseo, Helena A. Yu, P A Jänne, Andrea Ardizzoni · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.16_suppl.8643 · 研究领域：Lung Cancer Treatments and Mutations、Radiomics and Machine Learning in Medical Imaging、Cancer Immunotherapy and Biomarkers

8643 Background: With rapidly expanding first-line options for patients (pts) with EGFR -mutated non-small cell lung cancer (NSCLC), identifying biomarkers that may assist treatment selection is critical. The impact of EGFR amplification ( EGFR AMP ) on osimertinib outcomes is unclear. Methods: Pts with stage IV NSCLC and EGFR exon 19 deletions (ex19del) or the L858R mutation who received first-line osimertinib monotherapy at 5 centres across Italy and the United States and had undergone baseline next-generation sequencing (NGS) that included EGFR AMP assessment were included in this analysis. EGFR AMP was defined as an EGFR copy number (CN) ≥6. The predominantly amplified allele was inferred by INCOMMON, a biostatistical classifier, as previously described. Results: Among 473 pts, 81 (17.1%) had EGFR AMP . Compared to pts with non-amplified EGFR ( EGFR Non-AMP , n = 392), pts with EGFR AMP more frequently had TP53 co-mutations (80% vs 55%, p < 0.001) and baseline brain (51% vs 34%, p = 0.008), liver (26% vs 13%, p = 0.009), and bone metastasis (65% vs 51%, p = 0.03). When treated with osimertinib, pts with EGFR AMP achieved similar objective response rate (ORR) (88% vs 83%, p = 0.23), but shorter median progression-free survival (mPFS) (11.6 vs 19.0 months, HR 1.77, p < 0.0001) and overall survival (mOS) (34.0 vs 40.1 months, HR 1.40; p = 0.040). In a multivariable Cox-regression model, EGFR AMP retained its association with worse PFS (HR 1.36, p = 0.04), but not OS. E...