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Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK

Luke R G Pike1, Emily Miao1,2, Lillian A Boe3

  • 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|July 24, 2024
PubMed
Abstract

Insights

Adding upfront stereotactic radiosurgery (SRS) to tyrosine kinase inhibitors (TKIs) improved brain progression control in non-small cell lung cancer (NSCLC) patients with brain metastases (BM). Overall survival was not significantly impacted, but larger BM may benefit most from SRS.

Area of Science:

  • Oncology
  • Neurology
  • Radiotherapy

Background:

  • Newer tyrosine kinase inhibitors (TKIs) for EGFR- and ALK-driven NSCLC show high central nervous system (CNS) activity.
  • The role of upfront stereotactic radiosurgery (SRS) in patients with brain metastases (BM) eligible for CNS-penetrant TKIs remains debated due to limited data.

Purpose of the Study:

  • To evaluate the impact of upfront SRS combined with CNS-penetrant TKIs on outcomes for patients with EGFR- and ALK-driven NSCLC and BM.
  • To compare time-to-CNS progression and overall survival (OS) between TKI-only and TKI + SRS treatment groups.

Main Methods:

  • Retrospective analysis of TKI-naïve patients with EGFR/ALK-driven NSCLC and BM from seven US academic centers.
  • Patients received either CNS-penetrant TKIs alone or in combination with upfront SRS.
  • Time-to-CNS progression and OS were analyzed using multivariable models (Fine & Gray, Cox proportional hazards).

Main Results:

  • 317 patients were analyzed (200 TKI-only, 117 TKI + SRS); 79% received osimertinib, 19% alectinib.
  • Upfront SRS was associated with significantly improved time-to-CNS progression (HR 0.63) and local CNS control (HR 0.30).
  • Median OS was similar between groups (41 months TKI-only vs. 40 months TKI + SRS); patients with BM ≥1 cm showed greater benefit from SRS.

Conclusions:

  • Upfront SRS combined with CNS-penetrant TKIs improves time-to-CNS progression and local CNS control in NSCLC patients with BM.
  • Overall survival was not significantly improved by the addition of upfront SRS.
  • Patients with larger brain metastases (≥1 cm) may derive the most benefit from upfront SRS.

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