In a retrospective study (TURBO-NSCLC) reported in the Journal of Clinical Oncology, Pike et al found that the addition of upfront stereotactic radiosurgery (SRS) to central nervous system (CNS)-penetrant tyrosine kinase inhibitor (TKI) treatment prolonged time to CNS progression vs TKI treatment alone in TKI-naive patients with brain metastases from EGFR- and ALK-altered non–small cell lung cancer (NSCLC). No overall survival difference was observed.
Study Details
The study involved data on 317 patients treated at 7 U.S. centers between 2013 and 2022, including 200 receiving TKI therapy only and 117 receiving TKI/SRS. The most commonly used TKIs were osimertinib (79%) and alectinib (19%). The main outcomes of interest were time to CNS progression and overall survival.
Key Findings
Patients receiving TKI/SRS were more likely to have brain metastases measuring ≥ 1 cm (P < .001) and neurologic symptoms (P < .001) at presentation.
On multivariable analysis, TKI/SRS was associated with significantly improved time to CNS progression than TKI treatment alone (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.42–0.96, P = .033). The cumulative incidence of CNS progression was 17% vs 29% at 12 months and 34% vs 39% at 24 months, respectively.
Local CNS control was also significantly improved with TKI/SRS vs TKI (HR = 0.30, 95% CI = 0.16–0.55, P < .001); cumulative incidence of local progression was 5% vs 21% at 12 months and 9% vs 25% at 24 months, respectively. No significant difference was observed in distant CNS control (P = .09), with distant progression rates of 12% vs 8% at 12 months and 25% vs 14% at 24 months, respectively.
Median overall survival was 40 months (95% CI = 34 months to not reached) in the TKI/SRS group vs 41 months (95% CI = 35 months to not reached) in the TKI group (HR = 0.96, 95% CI = 0.64–1.44, P = .8).
Analysis among TKI/SRS vs TKI alone patients with metastases measuring ≥ 1 cm showed local progression rates of 6% vs 31% at 12 months and 11% vs 36% at 24 months (P < .001) and median CNS progression-free survival of 27 months vs 17 months (P = .013).
The investigators concluded, “The addition of upfront SRS to CNS-penetrant TKI improved time to CNS progression and local CNS control, but not overall survival, in patients with brain metastases from EGFR- and ALK-driven NSCLC. Patients with larger brain metastases (≥ 1 cm) may benefit the most from upfront SRS.”
Chad G. Rusthoven, MD, of the Department of Radiation Oncology, University of Colorado, Aurora, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
