1. Brain Metastases in EGFR- and ALK-Positive NSCLC: Outcomes of Central Nervous System-Penetrant Tyrosine Kinase Inhibitors Alone Versus in Combination With Radiation
- Author
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Fangdi Sun, Nathaniel J. Myall, Sumi Sinha, Rao Mushtaq, Steve Braunstein, Heather A. Wakelee, Seema Nagpal, Nicholas J. Thomas, Caroline E. McCoach, Erqi L. Pollom, Tejas Patil, Chad G. Rusthoven, D. Ross Camidge, and Chandler Yu
- Subjects
Central Nervous System ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Central nervous system ,Text mining ,Internal medicine ,Retrospective analysis ,medicine ,Humans ,In patient ,Protein Kinase Inhibitors ,Time to treatment failure ,Retrospective Studies ,Brain Neoplasms ,business.industry ,ALK-Positive ,respiratory tract diseases ,ErbB Receptors ,Radiation therapy ,medicine.anatomical_structure ,Mutation ,business ,Tyrosine kinase - Abstract
Introduction Management of central nervous system (CNS) metastases in patients with driver-mutated NSCLC has traditionally incorporated both tyrosine kinase inhibitors (TKIs) and intracranial radiation. Whether next generation, CNS-penetrant TKIs can be used alone without upfront radiation, however, remains unknown. This multi-institutional retrospective analysis aimed to compare outcomes in patients with EGFR- or ALK-positive NSCLC who received CNS-penetrant TKI therapy alone versus in combination with radiation for new or progressing intracranial metastases. Methods Data were retrospectively collected from three academic institutions. Two treatment groups (CNS-penetrant TKI alone versus TKI + CNS radiation therapy) were compared for both EGFR- and ALK-positive cohorts. Outcome variables included time to progression, time to intracranial progression, and time to treatment failure, measured from the date of initiation of CNS-penetrant TKI therapy. Results A total of 147 patients were included (EGFR n = 94, ALK n = 52, both n = 1). In patients receiving radiation, larger metastases, neurologic symptoms, and receipt of steroids were more common. There were no significant differences between TKI and CNS radiation therapy plus TKI groups for any of the study outcomes, including time to progression (8.5 versus 6.9 mo, p = 0.13 [EFGR] and 11.4 versus 13.4 mo, p = 0.98 [ALK]), time to intracranial progression (14.8 versus 20.5 mo, p = 0.51 [EGFR] and 18.1 versus 21.8 mo, p = 0.65 [ALK]), or time to treatment failure (13.8 versus 8.6 mo, p = 0.26 [EGFR] and 13.5 versus 23.2 mo, p = 0.95 [ALK]). Conclusions These results provide preliminary evidence that intracranial activity of CNS-penetrant TKIs may enable local radiation to be deferred in appropriately selected patients without negatively affecting progression.
- Published
- 2022
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