In brief
- Among 473 patients with metastatic EGFR-mutated NSCLC treated with first-line osimertinib, 81 (17.1%) had EGFR amplification, defined as an EGFR copy number of 6 or more at baseline sequencing.
- Response rates were similar, but median progression-free survival was 11.6 versus 19.0 months (hazard ratio 1.77, p < 0.0001) and median overall survival 34.0 versus 40.1 months (hazard ratio 1.40, p = 0.040).
- The association with worse outcomes was seen in patients with EGFR exon 19 deletions but not in those with L858R, and amplification of the mutant allele carried a worse outcome than amplification of the wild-type allele.
Background
Treatment options for EGFR-mutated NSCLC have expanded quickly, and the authors stated that identifying biomarkers that may assist treatment selection is critical. EGFR amplification is a candidate, and its impact on outcomes with osimertinib was described as currently unknown. Not every next-generation sequencing panel assesses it: the study’s own eligibility criterion was baseline sequencing that included an assessment of EGFR amplification.
Study design
The investigators included patients with metastatic EGFR-mutated NSCLC who received first-line osimertinib and had undergone baseline next-generation sequencing that assessed EGFR amplification. Amplification was defined as an EGFR copy number of 6 or more.
Findings
Among 473 patients, 81 (17.1%) had EGFR amplification. Compared with the 392 patients whose tumours were not amplified, they more frequently had TP53 co-mutations (80.0% versus 55.4%, p < 0.001) and more frequently had metastatic disease in the 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).
On osimertinib, the two groups had a similar objective response rate (88% versus 83%, p = 0.23). Median progression-free survival was shorter with amplification, at 11.6 months versus 19.0 months (hazard ratio 1.77, p < 0.0001), as was median overall survival, at 34.0 months versus 40.1 months (hazard ratio 1.40, p = 0.040).
Subgroups and copy number
EGFR amplification was consistently associated with worse progression-free survival regardless of TP53 co-mutation status. By mutation subtype, amplification was associated with worse progression-free and overall survival in patients with EGFR exon 19 deletions, but not in those with L858R. Within the amplified cases, a higher EGFR copy number correlated with inferior outcomes, and so did amplification of the mutant allele rather than the wild-type allele.
Resistance at progression
Among a subset of 113 patients reassessed by next-generation sequencing after osimertinib resistance, those with baseline EGFR amplification more frequently showed acquired MET alterations (29% versus 12%, p = 0.04).
What comes next
The authors concluded that EGFR amplification correlates with distinct clinical characteristics and worse outcomes on osimertinib monotherapy in EGFR-mutated NSCLC. What the paper reports are associations measured in patients who had already been treated, and it sets out no rule for assigning treatment by amplification status.
Sources
- Clinical Cancer Research. Clinical significance of EGFR amplification in patients with EGFR -mutated metastatic non-small cell lung cancer receiving first-line osimertinib (2026-07-14). doi.org
Featuring Lung Summit faculty
This study was co-authored by Lung Summit faculty Biagio Ricciuti.
This article was produced independently by the Lung Summit editorial team, without industry funding or input.
