ELIOS: A Multicenter, Molecular Profiling Study of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer
Zofia Piotrowska1, Myung-Ju Ahn2, Pei Jye Voon3
1Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Cancer Discovery
|March 6, 2026
Summary
Acquired resistance to osimertinib in advanced EGFR-mutant non-small cell lung cancer (NSCLC) involves common alterations like MET amplification and EGFR C797S. Tissue and plasma NGS reveal diverse resistance mechanisms, necessitating broad treatment strategies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- First-line osimertinib is a standard treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC).
- Understanding acquired resistance mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- To characterize acquired resistance mechanisms to first-line osimertinib in EGFR-mutant advanced NSCLC.
- To compare tumor biopsies pre-treatment and post-progression.
Main Methods:
- Prospective study (ELIOS, NCT03239340) of 154 patients with EGFR-mutant advanced NSCLC.
- Next-generation sequencing (NGS) on paired tissue biopsies (n=52) and matched tissue/plasma samples (n=51).
- Proteogenomic analysis (n=32 baseline, n=18 post-progression).
Main Results:
- Common acquired alterations included MET amplification (17%), CDKN2A/CDKN2B deletion (15%), MTAP deletion (13%), and EGFR C797S (13%).
- TROP2 expression was high at baseline and post-progression regardless of genetic alterations.
- 82% of patients with matched post-progression samples showed resistance alterations via NGS.
Conclusions:
- Tissue biopsies are challenging to obtain post-progression in NSCLC patients on targeted therapy.
- Acquired resistance mechanisms are heterogeneous, highlighting the need for broad-acting treatment strategies.
- Complementary roles of tissue and plasma NGS in identifying resistance mechanisms were demonstrated.
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