INNV-11. COMPLETE RESPONSE TO SELPERCATINIB IN A PATIENT WITH RECURRENT GLIOBLASTOMA AND RET AMPLIFICATION

Abstract

Abstract BACKGROUND Glioblastoma (GBM) is a malignant central nervous system tumor that remains largely incurable. Limited treatment options currently exist after disease progression on the standard of care first-line therapy. However, repurposing the use of approved therapies in patients with potentially targetable genomic alterations continues to be an emerging area of interest. Here, we present the first reported case of a patient with isocitrate dehydrogenase wild-type GBM with an underlying RET amplification who demonstrated a near-complete response (CR) while receiving therapy with the targeted RET inhibitor, selpercatinib. CLINICAL PRESENTATION A 48-year-old male with no significant past medical history presented with sudden onset of dizziness and confusion. Magnetic resonance imaging (MRI) revealed two rim enhancing lesions in the right parietal lobe and the patient underwent surgical resection with subsequent pathology revealing a GBM. Genomic analysis identified a RET amplification. After standard adjuvant therapy, the patient was treated with selpercatinib 160 mg twice daily as a continuous regimen with near CR on MRI after six weeks of treatment. The patient was continued on therapy for a total of eight months before having disease progression requiring discontinuation of selpercatinib and was then transitioned to the next line of therapy for disease stabilization. To better characterize the response, further whole-exome sequencing and analysis were performed on the original specimen. CONCLUSION Although selpercatinib is approved in RET-fusion positive lung and thyroid cancer, we present a remarkable case of a recurrent, RET-amplified GBM having a CR to selpercatinib. The case highlights the excellent blood-brain barrier penetration of selpercatinib, as well as its potential role in RET-amplified GBM. Larger biomarker-enriched studies are needed to confirm the results of this case report. However, given the rare incidence of RET alterations in GBM, findings from this report can help guide and support optimal treatment strategies for patients with RET-altered GBM.