Trial Overview

Conducted between May 2018 and March 2019, this crucial study involved 50 patients with a cumulative total of 184 CNS hemangioblastoma lesions. These participants were recruited from various clinical sites across the United States, Denmark, France, and the United Kingdom. Each patient received a daily dose of belzutifan at 120 mg until disease progression or unacceptable toxicity levels materialized. Notably, none of the patients had undergone prior systemic therapies, setting the stage for an accurate assessment of belzutifan’s effectiveness. The earlier findings already indicated a significant positive response from belzutifan, and this latest report adds an additional 16 months of follow-up data.

Key Insights and Efficacy Results

In this analysis, the median duration of follow-up was recorded at 38.0 months (with an interquartile range [IQR] of 36.7–40.1 months). Patients remained on treatment for a median duration of 37.4 months (IQR = 36.1–39.5 months).

Two distinct approaches were employed to evaluate the patients' responses: - **Approach 1:** This method assessed all lesions that were measurable (≥ 1 cm maximum diameter) or nonmeasurable at baseline. Among the 50 patients, an objective response was noted in 22 individuals (44%, 95% confidence interval [CI] = 30%-59%), with 4 patients (8%) achieving a complete response. Furthermore, an encouraging 46% of the participants displayed stable disease. The median duration of response is yet to be determined (95% CI = 30.9 months to not reached). - **Approach 2:** This approach focused solely on baseline lesions classified as measurable (≥ 1 cm maximum diameter). In this scenario, 19 out of 25 patients exhibited an objective response (76%, 95% CI = 55%-91%), with 1 patient (4%) completing the treatment successfully. Again, 20% of patients maintained stable disease, with the median response duration remaining undetermined (95% CI = 33.8 months to not reached).

Despite the promising results, some patients did experience grade ≥ 3 adverse events, with 23 (46%) affected. Specifically, grade 3 adverse events occurred in 19 patients (38%), predominantly manifesting as anemia (12%). Additionally, two cases of grade 4 adverse events (both retinal vein occlusion and embolism) were reported. Tragically, two patients' deaths were attributed to factors unrelated to the treatment—one due to suicide and the other due to multiple toxicities.

Conclusion

The research team concluded that **“Belzutifan demonstrated significant antitumor activity in CNS hemangioblastomas associated with VHL disease, showcasing sustained efficacy for over three years of treatment.”** This establishes belzutifan as a viable systemic treatment option for those battling the challenges of VHL disease-related CNS hemangioblastomas. This research not only enhances hope for patients dealing with this complex condition but also emphasizes the potential of belzutifan as a groundbreaking therapeutic agent in oncology. If you or someone you know is affected by VHL disease, this latest study could signal a beacon of hope in terms of treatment options!