Combined BBB-penetrant tyrosine kinase inhibitor and intracranial radiotherapy versus BBB-penetrant tyrosine kinase inhibitor alone for the treatment of EGFR-mutated non-small cell lung cancer patients with brain metastases

Purpose: This study was to determine whether combining blood-brain-barrier-penetrant tyrosine kinase inhibitor (TKI), osimertinib, with intracranial radiotherapy (TKI + RT) would confer benefits exceeding those of osimertinib alone (TKI-alone) in terms of treatment outcomes among non-small cell lung cancer (NSCLC) patients with brain metastases and epidermal growth factor receptor (EGFR) mutation. Methods This single-center retrospective study focused on gamma-knife radiosurgery (GKRS) and whole brain radiotherapy (WBRT). Treatment outcomes included intracranial local tumor control, intracranial distant tumor control and overall survival (OS) rates. Results This study included 567 brain metastases in 69 patients: TKI-alone (n = 38) and TKI + RT (n = 31) including GKRS (n = 25) and WBRT (n = 6). Intracranial local tumor control at 36 months was significantly higher in the TKI + RT than in the TKI-alone (77% vs. 23%; p < 0.001). Intracranial distant tumor control was significantly higher in the TKI + RT than in the TKI-alone (median survival: 23.2 ± 1.5 vs. 8.7 ± 0.2 months; p < 0.001). We observed no difference between the two cohorts in terms of OS (p = 0.271). T790M point mutation (HR = 0.359, p = 0.008) and TKI + RT (HR = 0.396, p = 0.010) were positively correlated with intracranial local tumor control. The number of brain metastases was negatively correlated with intracranial distant tumor control (HR = 2.253, p = 0.034) and OS (HR = 2.049, p = 0.019). Conclusions The efficacy of osimertinib therapy for NSCLC patients with brain metastases and EGFR mutation was enhanced by combining this treatment with intracranial radiotherapy. Benefits were observed in terms of intracranial local control and distant control rates; however, no benefits were observed in terms of OS. Further prospective studies will be required to confirm these findings.