Response to Selpercatinib in a Patient With Recurrent Glioblastoma and RET Amplification

Abstract

Glioblastoma (GBM) is a malignant central nervous system neoplasm that remains largely incurable. Limited treatment options currently exist after disease progression on 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. This report presents the first description of a patient with isocitrate dehydrogenase wild-type GBM with an underlying RET amplification who demonstrated a near-complete response while receiving therapy with the RET inhibitor selpercatinib. The case highlights the excellent blood-brain barrier penetration of selpercatinib, as well as its potential role in the management of RET-amplified GBM. Larger biomarker-enriched studies are needed to confirm the results of this case report. 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.

RET-Altered Cancers—A Tumor-Agnostic Review of Biology, Diagnosis and Targeted Therapy Activity

“…In a pan-cancer cohort, RET amplifications (defined as ≥6 copies of wild-type RET ) were detected in 0.16% (145/91,466) of tumor samples, including 0.13% (15/11,622) of NSCLC cases [ 88 ]. RET amplifications have been observed in several other tumor types, including hepatobiliary cancers [ 88 , 89 ], prostate cancer [ 88 ], breast cancer [ 77 ], glioblastoma [ 90 ], stomach adenocarcinoma [ 91 ], colorectal adenocarcinoma [ 91 ], and bladder urothelial carcinoma [ 91 ]. The clinical significance of RET amplifications and their correlation with increased RET protein expression have not been fully characterized.…”

“…In addition, a documented response to selpercatinib was observed in a patient with RET -amplified glioblastoma. Follow-up MRI at 3 months revealed near complete resolution of gadolinium-enhancing brain lesions, with a sustained response spanning over 8 months [ 90 ]. These reports underscore the potential of selpercatinib as a therapeutic option for patients with RET -amplified tumors, thus warranting further investigation and clinical exploration.…”