Updated findings from the Phase II LITESPARK-004 trial, published in The Lancet Oncology, demonstrate the sustained efficacy of belzutifan in treating von Hippel-Lindau (VHL) disease-associated central nervous system (CNS) hemangioblastomas. The study, which included 50 patients with CNS hemangioblastomas, showed clinically meaningful activity of belzutifan with over three years of follow-up.
The trial enrolled patients between May 2018 and March 2019 across multiple sites in the United States, Denmark, France, and the United Kingdom. Participants received 120 mg of belzutifan once daily until disease progression or unacceptable toxicity. All patients were treatment-naive regarding systemic therapies. The primary outcome was objective response as assessed by an independent review committee.
Sustained Antitumor Activity
With a median follow-up of 38.0 months (IQR = 36.7–40.1 months) and a median treatment duration of 37.4 months (IQR = 36.1–39.5 months), belzutifan demonstrated durable antitumor activity. Using an approach that evaluated all measurable and non-measurable lesions at baseline, 44% of patients (95% CI = 30%–59%) achieved an objective response, including complete responses in 8% of patients. An additional 46% of patients experienced stable disease. The median duration of response was not reached (95% CI = 30.9 months to not reached).
An alternative assessment, focusing only on baseline lesions with a measurable solid component, showed an objective response rate of 76% (95% CI = 55%–91%), with a complete response rate of 4%. Stable disease was observed in 20% of this subgroup. Again, the median duration of response was not reached (95% CI = 33.8 months to not reached).
Safety Profile
Grade ≥ 3 adverse events were reported in 46% of patients. The most common Grade 3 adverse event was anemia (12%). Grade 4 adverse events occurred in 4% of patients, including retinal vein occlusion and embolism. Two deaths occurred during the study due to suicide and multiple toxicities; however, neither was considered treatment-related.
Expert Commentary
The study investigators concluded that belzutifan exhibits meaningful and sustained antitumor activity in VHL disease-associated CNS hemangioblastomas, supporting its use as a systemic treatment option. According to Othon Iliopoulos, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, these results reinforce belzutifan's potential in managing VHL disease-related CNS tumors.
