BBB-penetrant tyrosine kinase inhibitor plus intracranial radiotherapy vs BBB-penetrant TKI alone in Asians with EGFR-mutated lung adenocarcinoma and brain metastases

BACKGROUND: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), penetrates the blood-brain barrier and provides intracranial tumor control in non-small-cell lung cancer (NSCLC). This study investigated whether combining osimertinib with intracranial radiotherapy (RT) improved outcomes in the patients with EGFR-mutant lung adenocarcinoma and brain metastases. METHODS: This is a retrospective analysis included patients who took osimertinib accompanying with or without RT between 2014 and 2022 from a single tertiary medical center. At least one session of magnetic resonance imaging and clinical follow-up after treatment. Outcomes assessed were intracranial local control, intracranial distant control, and overall survival (OS). Kaplan-Meier curves were used for outcome demonstration. Cox regression analysis was also used to identify independent predictors from age, gender, smoking, characteristics of brain metastases, KPS, gene types (presence of T790M), and radiation modalities. RESULTS: A total of 567 brain metastases from 69 patients were enrolled: TKI alone (n = 38) and TKI + RT (n = 31). Intracranial local control was significantly higher with TKI+RT compared with TKI alone (77% vs 23%; p < 0.01) at 3-year follow-up. Intracranial distant control was also longer in the TKI + RT group (23.2 vs 8.7 months in median; p < 0.01). No significant difference in OS was observed between the two groups ( p = 0.27). Multivariable analysis demonstrated that the presence of T790M mutation ( p = 0.01) and TKI + RT ( p = 0.01) were associated with improved intracranial local control, while TKI + RT was also associated with improved intracranial distant control ( p = 0.03). CONCLUSION: The addition of RT to osimertinib enhanced intracranial local and distant control in the patients with EGFR-mutant lung adenocarcinoma and brain metastases, although no survival benefit was observed. Prospective studies are warranted to validate these findings.