Intracranial Outcomes of De Novo Brain Metastases Treated With Osimertinib Alone in Patients With Newly Diagnosed EGFR-Mutant NSCLC

Author(s): Brandon S. Imber, MD, MA1; Ryka Sehgal, MD2; Rachel Saganty, MD1; Anne S. Reiner, MPH3; A. Turan Ilica, MD4; Emily Miao, PharmD1; Bob T. Li, MD5; Gregory J. Riely, MD5; Helena A. Yu, MD5; Katherine S. Panageas, DrPH3; Robert J. Young, MD4; Luke R.G. Pike, MD, DPhil1; Nelson S. Moss, MD1
Source: https://doi.org/10.1016/j.jtocrr.2023.100607
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Although Osimertinib in another trial (article from a previous month) had also impressive response first-line osimertinib initiation of 25 days. In total, 136 previously untreated brain metastases were tracked from baseline. Overall, 105 lesions (77.2%) had complete response and 31 had partial response reflecting best objective response of 100%.

INTRODUCTION

Patients with EGFR-mutant NSCLC have a high incidence of brain metastases. The EGFR-directed tyrosine kinase inhibitor osimertinib has intracranial activity, making the role of local central nervous system (CNS)-directed therapies, such as radiation and surgery, less clear.

METHODS

Patients with EGFR-mutant NSCLC and brain metastases who received osimertinib as initial therapy after brain metastasis diagnosis were included. Individual lesion responses were assessed using adapted RANO-BM criteria. CNS progression and local progression of brain metastasis from osimertinib start were analyzed using cumulative incidence treating death as a competing risk. Overall survival was estimated using Kaplan-Meier methodology.

RESULTS

There were 36 patients who had a median interval from brain metastasis diagnosis to first-line osimertinib initiation of 25 days. In total, 136 previously untreated brain metastases were tracked from baseline. Overall, 105 lesions (77.2%) had complete response and 31 had partial response reflecting best objective response of 100%. Best response occurred at a median of 96 days (range: 28–1113 d) from baseline magnetic resonance imaging. This reflects a best objective response rate of 100%. Two-year overall survival was 80%. CNS progression rates at 1-, 2-, and 3-years post-osimertinib were 21%, 32%, and 41%, respectively. Lesion-level local failure was estimated to be 0.7% and 4.7% at 1- and 2-years post-osimertinib, respectively. No clinicodemographic factors including brain metastasis number were associated with post-osimertinib progression.

CONCLUSIONS

Intracranial response to osimertinib is excellent for patients with EGFR-mutant NSCLC with de novo, previously untreated brain metastases. Very low local failure rates support a strategy of upfront osimertinib alone in selected patients.

Author Affiliations

1Department of Radiation Oncology and Multidisciplinary Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, New York;2Department of Neurosurgery and Multidisciplinary Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, New York;3Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York;4Division of Neuroradiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;5Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York and Weill Cornell Medical College, New York, New York

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