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 30) correlated with a stepwise reduction of mPFS (19.0, 16.7, 10.3, and 8.7 months, respectively; log-rank p < 0.001) and mOS (40.1, 37.5, 38.8, and 15.3 months, respectively; log-rank p = 0.02). Moreover, amplification of the mutant allele, as opposed to wild-type amplification, correlated with inferior mPFS (8.3 vs 12.1 months, HR 2.72, p = 0.002) and mOS (17.3 vs 39.7 months, HR 2.08, p = 0.046). Among pts with paired NGS before and after acquired osimertinib resistance (n = 113), those with baseline EGFR AMP more frequently showed acquired MET alterations (29% vs 12%, p = 0.04). Conclusions: EGFR AMP is associated with distinctive characteristics and worse outcomes to osimertinib among pts with stage IV EGFR -mutated NSCLC.
Federico et al. (Thu,) studied this question.