Impact of Genomic Subtype on Intracranial Outcomes in Treatment-naive EGFR mutant NSCLC with Osimertinib (IGnITE).

Abstract

IntroductionBrain metastases (BM) causes significant morbidity and mortality in epidermal growth factor (EGFR) mutated non-small cell lung cancer (NSCLC). The effect of EGFR alteration subtypes on CNS-specific outcomes is poorly defined.MethodsPatients with EGFR-mutated NSCLC and BM treated with firstline osimertinib with or without SRS were retrospectively identified from 11 institutions. The primary endpoint was time to CNS progression. Time-to-event outcomes were analyzed using Kaplan-Meier methods. Hazard ratios were estimated with Cox proportional hazards models. Fine Gray models were used for competing risk endpoints.ResultsBetween 2016 and 2024, 470 patients were identified with the following alterations: exon 19 deletion (57%), L858R (33%), and atypical mutations (9.6%). At 24 months, cumulative incidence of CNS progression was 30% (95% CI: 25%-36%) for exon 19 deletions, 47% (95% CI: 39%-55%) for L858R, and 76% (95% CI: 59%-87%) for atypical mutations (pConclusionPatients with atypical and L858R EGFR mutations had significantly worse CNS outcomes compared to those with exon 19 deletions. Upfront SRS reduced the risk of CNS progression, with the greatest benefit in patients with atypical alterations. EGFR subtype may help identify patients who benefit from SRS.