ArticleThe oncologist2026
Clinical outcomes of HIF-2α inhibition in Von Hippel-Lindau disease: a multicenter real-world study.
Article in The oncologist, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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13 authors.
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Abstract
BACKGROUND AND
objectiveManagement of von Hippel-Lindau (VHL) disease is challenging due to multisystem involvement and limited systemic treatment options. Belzutifan has shown promising efficacy in clinical trials; however, real-world data remain limited. We aimed to evaluate its effectiveness and safety in a real-world cohort.
methodsWe conducted a retrospective study of 59 patients with VHL disease treated with belzutifan between August 2021 and January 2026. Objective response rates (ORR) for renal cell carcinoma (RCC), central nervous system hemangioblastomas (CNS HB), and pancreatic neuroendocrine tumors (pNET) were assessed by an independent radiologist. Retinal hemangioblastoma outcomes were evaluated through ophthalmology records by chart review.
resultsMedian follow-up was 29 months. ORR was 27.6%, 39.6%, and 85.7% for RCC, CNS HB, and pNET, respectively. Among 13 patients with retinal hemangioblastomas (20 eyes), 17 eyes (85%) showed improvement. At data cutoff, 47 patients (79.6%) remained on treatment, while 12 (20.3%) discontinued (7 due to adverse events, 3 to disease progression, and 2 to other reasons). The most common adverse event was anemia (86.4%). Grade ≥3 adverse events occurred in 10 patients (16.9%). The procedure rate per patient-year decreased from 0.35 in the 3 years prior to treatment to 0.08 during follow-up (Incidence Rate Ratio, 0.23; 95% CI, 0.12-0.47; P < .001).
conclusionsBelzutifan demonstrated efficacy across VHL-associated lesions, with a favorable safety profile. Most adverse events were grade 1-2. A reduction in procedure rate was observed after treatment initiation.
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