Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
Impact of Genomic Subtype on Intracranial Outcomes in Treatment-naive EGFR mutant NSCLC with Osimertinib (IGnITE).
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Miao Emily, Wo Emily, Boe Lillian, Lee James, Walch Henry, Yu Helena, Parker Mitchell, Imber Brandon, Chiang Jennifer, Hui Caressa, Myall Nathaniel, Pollom Erqi, Ni Lisa, Braunstein Steve, Hadley Christine, Matsui Jennifer, Palmer Joshua, Khandekar Melin, Marciscano Ariel, Shih Helen, Lee Albert, Chen Lanyi Nora, Shu Catherine A, Wang Tony, Boor Ian, Patil Tejas, Camidge D Ross, Messing Ian, Lebow Emily, Akdemir Eyub, Kotecha Rupesh, Carey Kelsey, Shi Wenyin, Khoja Lama, Sahgal Arjun, Soliman Hany, Rusthoven Chad G, George Pike Luke Roy
Аннотация
INTRODUCTION: Brain 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.
METHODS: Patients 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.
RESULTS: Between 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 (p<0.001). In multivariable models, CNS progression was higher among patients with atypical alterations (HR 4.33, 95% CI: 2.72-6.91) and L858R mutations (HR 1.68, 95% CI: 1.27-2.23) compared with exon 19 deletions. Stratified outcomes for exon 19, L858R, and atypical mutations were similar across local and distant CNS progression, and neurological mortality. Upfront SRS was associated with improved CNS outcomes, with greatest benefit in patients with atypical alterations.
CONCLUSION: Patients 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.
METHODS: Patients 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.
RESULTS: Between 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 (p<0.001). In multivariable models, CNS progression was higher among patients with atypical alterations (HR 4.33, 95% CI: 2.72-6.91) and L858R mutations (HR 1.68, 95% CI: 1.27-2.23) compared with exon 19 deletions. Stratified outcomes for exon 19, L858R, and atypical mutations were similar across local and distant CNS progression, and neurological mortality. Upfront SRS was associated with improved CNS outcomes, with greatest benefit in patients with atypical alterations.
CONCLUSION: Patients 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.