A comparative study of preclinical and clinical molecular imaging response to EGFR inhibition using osimertinib in glioblastoma.

Background: To demonstrate the potential value of F-fluorodeoxyglucose positron emission tomography (F-FDG PET) as a rapid, non-invasive metabolic imaging surrogate for pharmacological modulation of EGFR signaling in EGFR-driven GBM, we synchronously conducted a preclinical imaging study using patient-derived orthotopic xenograft (PDOX) models and validated it in a phase II molecular imaging study in recurrent GBM (rGBM) patients using osimertinib.

Methods: A GBM PDOX mouse model study was performed concurrently with an open-label, single-arm, single-center, phase II study of osimertinib (NCT03732352) that enrolled 12 patients with rGBM with EGFR alterations. Patients received osimertinib daily and 3 F-FDG PET scans: two 24 h apart prior to dosing, and one 48 h after dosing.

EGFR, the Lazarus target for precision oncology in glioblastoma.

The Lazarus effect is a rare condition that happens when someone seemingly dead shows signs of life. The epidermal growth factor receptor (EGFR) represents a target in the fatal neoplasm glioblastoma (GBM) that through a series of negative clinical trials has prompted a vocal subset of the neuro-oncology community to declare this target dead. However, an argument can be made that the core tenets of precision oncology were overlooked in the initial clinical enthusiasm over EGFR as a therapeutic target in GBM.