Retrospective study of clinical significance of EGFR amplification in patients receiving first-line osimertinib for EGFR-mutated mNSCLC

With rapidly expanding treatment options for EGFR-mutated non-small cell lung cancer (NSCLC), identifying biomarkers that may assist in treatment selection is important. A multinational retrospective study evaluated EGFR amplification (EGFR^AMP) as biomarker in patients receiving first-line osimertinib for EGFR-mutated metastatic NSCLC. EGFR^AMP was defined as an EGFR copy number ≥6. Among 473 patients, 81 (17.1%) had EGFR^AMP. Compared with the 392 patients with non-amplified EGFR, these patients frequently had TP53 comutations (80% versus 55.4%; p<0.001) and brain (50.6% versus 34.3%; p=0.008), liver (25.9% versus 13.5%; p=0.009), and bone (65.4% versus 51.3%; p=0.028) metastases. On first-line osimertinib, patients with EGFR^AMP achieved similar objective response rate (88% versus 83%; p=0.23) but shorter median progression-free survival (11.6 versus 19 months; HR 1.77; p<0.0001) and overall survival (34 versus 40.1 months; HR 1.40; p=0.040). EGFR^AMP was associated with worse PFS and OS in patients with EGFR exon 19 deletion but not in those with EGFR L858R. Among EGFR^AMP cases, a higher EGFR copy number and amplification of the mutant allele, as opposed to wild-type amplification, correlated with inferior outcomes. The authors conclude that EGFR^AMP is associated with distinct characteristics and worse outcomes on first-line osimertinib among patients with EGFR-mutated metastatic NSCLC.