CTNI-71. BELZUTIFAN FOR VON HIPPEL-LINDAU DISEASE-RELATED CENTRAL NERVOUS SYSTEM (CNS) HEMANGIOBLASTOMAS: SUBGROUP OF PHASE 2 LITESPARK-004 STUDY

Abstract

Abstract The HIF-2α inhibitor belzutifan is approved for von Hippel-Lindau (VHL) disease–associated renal cell carcinoma (RCC), CNS hemangioblastomas, or pancreatic neuroendocrine tumors not requiring immediate surgery based on results of the phase 2 LITESPARK-004 study (NCT03401788). Updated results in patients with CNS hemangioblastomas are presented. Adults with VHL disease based on germline VHL alteration, ≥ 1 measurable RCC tumor, and no prior systemic anticancer therapy received oral belzutifan 120 mg once daily. End points included ORR, DOR, and PFS per RECIST v1.1 and safety. CNS hemangioblastomas were assessed using 2 approaches: (1) measurable (≥ 1 cm) and/or nonmeasurable lesions at baseline based on total size of solid and associated cystic components, if present, and (2) only measurable solid lesions at baseline. Of 61 patients, 50 (82%) had ≥ 1 CNS hemangioblastoma evaluable at baseline; 19/50 (38%) underwent ≥ 1 CNS-related procedure ≤ 3 years before starting belzutifan. Median follow-up was 38.0 months (range, 36.1-46.1). ORR was 44%. Median DOR was not reached (NR; range, 3.7+ to 38.7+ months). DCR was 90%. Median PFS was NR (95% CI, 38 months-NR). 25/50 (50%) had ≥ 1 measurable, solid-only CNS hemangioblastoma. For these patients, ORR was 76%. Median DOR was NR (range, 3.7+ to 38.7+ months). DCR was 96%. Median PFS was NR (95% CI, 36 months-NR). 2/50 patients (4%) underwent 3 procedures for CNS hemangioblastomas after starting treatment with belzutifan. Two patients (3%) discontinued treatment due to treatment-related AEs (grade 2 intracranial hemorrhage and grade 1 dizziness). RESULTS: showed consistent and durable antitumor activity in patients with CNS hemangioblastomas. Belzutifan induced shrinkage of CNS hemangioblastomas with or without the presence of associated cysts. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.