BIOM-44 - Improved overall survival of recurrent glioblastoma (GBM) patients with EGFR amplification and EGFR vIII mutations treated with osimertinib: a retrospective review

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with an overall survival (OS) of 14.6-23 months in clinical trial patients and 11 months for the real world population. There is no uniform standard of care for recurrent GBM (rGBM) patients. EGFR amplification and EGFRvIII mutations are common in GBM and are potential targets with EGFR tyrosine kinase inhibitors (EGFR-TKI). Osimertinib, a third-generation EGFR-TKI, effectively penetrates the blood brain barrier and is FDA-approved for non-small cell lung cancer. We conducted a retrospective review of rGBM patients with EGFR amplification and EGFRvIII mutations who received osimertinib in addition to other therapies such as bevacizumab, irinotecan, tumor-treating fields, and salvage radiation at recurrence. The primary outcome was OS. Secondary outcomes included recurrence free survival (RFS), overall survival after initiation of osimertinib (rOS), and adverse events (AE). Statistical analysis utilized the Kaplan-Meier estimate. AE were defined by the Common Terminology Criteria for Adverse Events Version 5.0. Twenty-seven patients (17 males) with a median age of 59 years (range: 29-75) were identified. All except one patient were IDH1-wild type (92.9%). MGMT promoter statuses included ten methylated (35.71%) and 11 unmethylated patients (39.29%). The median time on osimertinib was 5.1 months. The median OS was 28 months (95% CI 24, NA). Following osimertinib initiation, the median RFS was 6.4 months (95% CI 5.1, NA), and the median rOS was 12 months (95% CI 8.4, NA). AEs included grade I/II rash (44.4%), grade I/II diarrhea (40.7%), grade III leukopenia (18.5%), and grade III thrombocytopenia (11.1%). The data suggests that osimertinib improves the OS of rGBM patients with manageable and reversible AEs. Despite the limitations of a retrospective study and small sample size, osimertinib is a promising targeted therapy for rGBM. Further research is warranted in a clinical trial to evaluate this treatment prospectively.