MMAP-11 VOLUMETRIC STUDY OF BRAIN METASTASES IN EGFR-POSITIVE NSCLC TREATED WITH OSIMERTINIB WITH OR WITHOUT CNS-DIRECTED RADIATION THERAPY

BACKGROUND: In patients with brain metastases (BM) from EGFR-positive non-small cell lung cancer (NSCLC), recent data indicated that treating with CNS-penetrant tyrosine kinase inhibitors such as osimertinib may enable deferring radiotherapy (RT) in select patients. The purpose of this study was to describe the radiographic response of newly diagnosed BM to osimertinib with or without stereotactic radiosurgery or whole brain radiotherapy, to identify parameters that may guide early versus delayed salvage RT. METHODS: In this single-institution retrospective study, 35 patients with 186 newly diagnosed BM started on osimertinib between 2014 and 2020 were reviewed. BM with tumor volume ≥ 0.1 cm(3) were included in the volumetric analyses (N=106 BM). Survival was estimated with the Kaplan-Meier method, and univariable analysis was performed using log-rank tests. Cox proportional hazards was used for multivariable analyses for local control (LC), distant brain failure (DBF), and overall survival (OS). RESULTS: Of the 35 patients, 8 (23%) received osimertinib alone. Median follow-up was 29 months. The 1- and 2-year LC rates were 94% and 86%. The 1- and 2-year OS rates were 89% and 66%. Median time to DBF was 24 months. Patients treated with osimertinib and RT were more likely to have a significant radiographic volumetric response at early follow-up (4-12 weeks after treatment initiation) compared to osimertinib alone (median volumetric response of –80% vs. –41%, p=0.05). On per lesion analysis, early volumetric response of ≥ 80% was associated with improved LC (3-year LC 98% vs 72%, p=0.04). CONCLUSIONS: The combination of osimertinib and CNS RT is associated with greater early volumetric response in patients with BM from EGFR-positive NSCLC compared to osimertinib alone. BM with significant initial radiographic response remain well-controlled in the long term. Patients whose BM demonstrate limited initial volumetric response may benefit from targeted RT to provide long term control.