Combined stereotactic radiosurgery and tyrosine kinase inhibitor therapy versus tyrosine kinase inhibitor therapy alone for the treatment of non-small cell lung cancer patients with brain metastases

Objective: Whether combined radiation and tyrosine kinase inhibitor (TKI) therapy in non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) and epidermal growth factor receptor (EGFR) mutations confers additional benefits over TKI therapy alone remains a matter of debate. The goal of this study was to compare outcomes between combined TKI therapy with stereotactic radiosurgery (SRS) versus TKI therapy alone in NSCLC patients with BMs and EGFR mutations.

Methods: Consecutive cases of NSCLC patients with EGFR mutations and BMs treated with TKIs were selected for inclusion in this study. Patients were categorized into two groups based on SRS: TKI therapy alone (group I) and combined SRS and TKI therapy (group II). Patients who had SRS or TKI as salvage therapy and those with prior radiation treatment for BMs were excluded. Tumor control (< 10% increase in tumor volume) and overall survival (OS) rates were compared using Kaplan-Meier analyses. Independent predictors of tumor control and OS were identified using multivariable Cox regression analyses.

Results: The study cohort comprised 280 patients (n = 90 in group I and n = 190 in group II). Cumulative tumor control rates were higher in group II than in group I (79.8% vs 31.2% at 36 months, p < 0.0001). Cumulative OS rates were comparable between groups I and II (43.8% vs 59.4% at 36 months, p = 0.3203). Independent predictors of tumor control were older age (p < 0.01, HR 1.03), fewer BMs (p < 0.01, HR 1.09), lack of extracranial metastasis (p < 0.02, HR 0.70), and combined SRS and TKI therapy (p < 0.01, HR 0.25). Independent predictors of OS were fewer BMs (p < 0.01, HR 1.04) and a higher Karnofsky Performance Status score (p < 0.01, HR 0.97).

Conclusions: Although the OS rate did not differ between TKI therapy with and without SRS, the addition of SRS to TKI therapy resulted in improvement of intracranial tumor control. The lack of effect on survival rate with the addition of SRS may be attributable to extracranial disease progression. The addition of SRS to TKI therapy is recommended for intracranial disease control in NSCLC patients with BMs and EGFR mutations. Potential benefits may include prevention of neurological deficits and seizures. Future prospective studies may help clarify the clinical outcome benefits of SRS in these patients.