Upfront Treatment With Osimertinib vs. Osimertinib and Radiotherapy for Patients With EGFR-Positive Non-Small Cell Lung Cancer Brain Metastases

Abstract

<h3>Purpose/Objective(s)</h3> Given the improved central nervous system penetration of 3^rd generation tyrosine kinase inhibitors, such as osimertinib, the role of upfront radiation therapy (RT) in the setting of brain metastases (BM) has been brought into question. We sought to retrospectively evaluate outcomes at our institution for patients with EGFR-positive NSCLC treated with osimertinib as the upfront treatment for new or progressing BM versus osimertinib in combination with intracranial RT. <h3>Materials/Methods</h3> This single-institution retrospective analysis of EGFR-positive NSCLC with new or progressing BM included a total of 92 patients with 405 BM treated between 2013 to 2021 and followed until July 2021. Two BM treatment groups were evaluated: (1) patients treated with upfront osimertinib alone (n=58), and (2) patients treated with osimertinib combined with RT [either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) prior or concurrently with osimertinib (n=34)]; both groups began treatment within 2 months of BM diagnosis. Time-to-event analysis was conducted with the Kaplan-Meier (KM) method, and outcomes included distant intracranial control (DIC), local control (LC), and overall survival (OS). Cox proportional hazards model was utilized for multivariate analysis (MVA) to identify correlations of clinical outcomes. <h3>Results</h3> Median follow-up from BM diagnosis was 13.2 months (0.8-48.9 months). Of the patients treated with osimertinib and RT, 17 were treated with SRS and 17 with WBRT. No significant differences in age (p=0.96), gender (p=0.42), DS-GPA (p=0.73), KPS (p=0.54, number (p=0.52) or volume (p=0.29) of BM, SRS dose (p=0.44), or number of systemic metastases (p=0.88) were noted between groups. No difference between osimertinib vs osimertinib and RT groups was noted for 12 month KM rates of DIC 84.9% and 68.7% (p=0.80); LC 99.6% and 93.1% (p=0.31); and OS 66% and 73.5% (p=0.). Of the 58 patients treated with upfront osimertinib, 19 patients with 77 lesions eventually required radiation for intracranial progression with 62 of those lesions being treated with SRS. Upon MVA, higher KPS (p=.001) and DS-GPA (p=0.002) were associated with increased OS and systemic metastasis at time of treatment with worse OS (p=0.001). <h3>Conclusion</h3> The results of this study support other preliminary data suggesting that upfront osimertinib alone may provide sufficient intracranial control to allow RT to be deferred until further intracranial progression. Prospective trials are needed to further guide treatment.