Genomic Profiling of Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer Post-Progression on First-Line Osimertinib: Phase II ORCHARD Study - PubMed
5 days ago
- #NSCLC
- #Genomic Profiling
- #Osimertinib
- Osimertinib is the standard first-line treatment for EGFR-mutated NSCLC.
- The ORCHARD study explored molecular profiles post-progression on osimertinib to guide second-line treatments.
- Patients were allocated into three groups based on tumor molecular profiles via NGS.
- TP53 and MDM2/4 alterations were found in 85% of tumors and were mutually exclusive.
- Resistance alterations were detected in 87% of samples, with 46% showing multiple resistance mechanisms.
- PI3K pathway, SOX2, and MYC alterations were common in histologically transformed tumors.
- Differential EGFR mutation patterns were observed between L858R and exon 19 deletion tumors.
- The study suggests heterogeneous resistance to osimertinib, advocating for combination therapies.