2189 - Outcomes of SRS for Isolated CNS Progression Among Patients with EGFR-Mutated NSCLC Receiving Osimertinib
Presenter(s)
M. D. Riina1, I. Messing1, M. Berger1, L. C. Linkowski2, X. Wang3, S. Shyamsundar1, H. G. Hubbeling1, G. Kurtz1, C. Jackson4, S. Mohan5, C. Aggarwal6, M. Alonso-Basanta2, J. D. Bradley2, R. Cohen6, and E. S. Lebow2; 1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 2Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 3Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, 4Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, 5Department of Radiology, University of Pennsylvania, Philadelphia, PA, 6Department of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA
Purpose/Objective(s): Isolated CNS progression (ICP) is a well-characterized pattern of failure in patients with EGFR-mutated (EGFRm) NSCLC receiving osimertinib. Stereotactic radiosurgery (SRS) may control CNS disease and prolong time to next line systemic therapy. Analyses of prognostic factors are needed to guide therapy selection and clinical decision making.
Materials/Methods: We performed a single institution retrospective cohort study of patients with EGFRm NSCLC receiving osimertinib monotherapy treated with SRS for ICP, defined as new or progressive brain metastases (BM) without evidence of systemic progression in the preceding month. Overall survival (OS) and central nervous system progression free survival (CNS PFS) were estimated from completion of SRS until progression or last contact using the Kaplan Meier method. The cumulative incidence function was used to estimate incidences of CNS progression and next line systemic therapy initiation. Cox proportional hazards models were used to assess clinically relevant factors for OS. Fine-Gray competing risks models were used to assess risk factors for CNS progression and next line systemic therapy initiation.
Results: From 1/2015 – 8/2025, 31 patients met inclusion criteria. Median age was 63 (range 48-80), 65% were white, 68% were female, and 58% were never smokers. Most had either exon 19 deletions (32%) or L858R mutations (42%). 81% had BM at initial diagnosis of metastatic disease and 29% had prior cranial RT. 13% received chemotherapy with osimertinib at initial diagnosis of metastatic disease. Median number of lesions treated with SRS was 3 (range 1-28). 12- and 24-month OS were 76% and 39%. 12- and 24-month CNS PFS were 28% and 9%. Median time to additional CNS progression was 6.5 months (IQR 3.8-21.8 months). 24-month cumulative incidences of additional CNS progression, local CNS progression, distant CNS (out of field) progression, and leptomeningeal (LMD) progression were 72%, 17%, 70%, and 30%. 12- and 24-month cumulative incidences of next line systemic therapy initiation were 24% and 33%. Median time to next systemic therapy was not reached. Risk factors associated with worse OS were KPS =80 at ICP (HR=7.8 [95%CI: 2.2-27.3], p<0.01) and =5 lesions treated with SRS (HR=4.2 [95%CI: 1.4-12.6], p<0.05). Risk factors associated with higher incidence of additional CNS progression included receipt of upfront chemotherapy with osimertinib (HR=3.5 [95%CI:1.6-7.6], p<0.01) while treatment of =5 lesions with SRS approached significance (HR=2.1 [95%CI: 0.9-5.1], p=0.1). Specific driver mutation (L858R, exon19 deletion, or other/compound mutations) was not associated with OS, additional CNS progression, or next line systemic therapy.
Conclusion: In patients with EGFRm NSCLC with ICP on osimertinib, SRS can control intracranial disease and delay next line systemic therapy in a subset of patients, although risk of CNS relapse remains high. Prognostic factors such as intracranial disease burden and KPS may help guide patient selection.