Comparative efficacy of osimertinib with and without radiation therapy in EGFR-mutated non-small cell lung cancer with brain metastases.

Abstract

8556 Background: Osimertinib has demonstrated efficacy in managing brain metastases in EGFR-mutated non-small cell lung cancer (NSCLC). However, the optimal approach—using CNS-penetrant tyrosine kinase inhibitor (TKI) therapy alone versus combining it with radiation therapy—remains uncertain. This study examines whether Osimertinib combined with radiation provides superior intracranial control and outcomes compared to Osimertinib alone. Methods: Patients aged ≥18 years with NSCLC and brain metastases diagnosed between January 2010 and December 2024 were identified via the TriNetX Research Network. Two cohorts were analyzed: those receiving Osimertinib with stereotactic radiation or radiosurgery within six months (cohort 1) and those without radiation (cohort 2). Propensity score matching balanced baseline characteristics. Outcomes included survival, hospitalization rates, CNS complications, and second-line treatment initiation. A Kaplan-Meier analysis evaluated survival and mortality while a Cox proportional hazards model assessed the effects of covariates. Results: A total of 76,474 NSCLC patients were identified, 13,377 had brain metastases, and 743 received Osimertinib. Kaplan-Meier analysis indicated lower mortality in cohort 1 at 3 years (HR = 0.674, p = 0.0029), 5 years (HR = 0.719, p = 0.0091), and overall (HR = 0.709, p = 0.0063). CNS complications (risk difference = 20.28%, p < 0.0001) were higher in cohort 1, with 11 patients diagnosed with radiation necrosis after treatment, representing a 5.28% risk. Additionally more people in cohort 1 developed interstitial lung disease (risk difference = 9.1%, p=0.0016). Second-line treatment initiation (HR = 1.741, p = 0.0166) was also higher in cohort 1. Key predictors of increased mortality included hypertension (HR = 1.366, p = 0.0047), bone metastases (HR = 1.608, p < 0.0001), and liver metastases (HR = 1.319, p = 0.0408). Stereotactic radiosurgery in particular was associated with a lower hazard ratio (HR = 0.487, p = 0.0031). Conclusions: Combining Osimertinib with stereotactic radiation or radiosurgery improves survival in NSCLC with brain metastases but may increase CNS complications and second-line treatment rates. These findings highlight the need to balance survival benefits with treatment risks to optimize patient care.