As reported in The Lancet Oncology by Iliopoulos et al, updated findings from the phase II LITESPARK-004 trial support the efficacy of belzutifan in patients with von Hippel-Lindau (VHL) disease–associated CNS hemangioblastomas.
Study Details
In the study, 50 patients with CNS hemangioblastomas (total of 184 lesions) enrolled between May 2018 and March 2019 from sites in the United States, Denmark, France, and United Kingdom received belzutifan at 120 mg once daily until disease progression or unacceptable toxicity. Patients had received no prior systemic therapy. The primary outcome measure was objective response on independent review committee assessment. The initial report from the study showed clinically meaningful activity of belzutifan; the current report includes 16 additional months of follow-up.
Key Findings
Median follow-up was 38.0 months (interquartile range [IQR] = 36.7–40.1 months) in this analysis. The median duration of treatment was 37.4 months (IQR = 36.1–39.5 months).
Response was assessed using two approaches. In approach 1, all measurable (≥ 1 cm maximum diameter) or nonmeasurable lesions at baseline were evaluated, including both the solid lesion and associated cystic component if present. On this approach, 22 (44%, 95% confidence interval [CI] = 30%–59%) of 50 patients had objective response, with complete response in 4 (8%). An additional 23 patients (46%) had stable disease. Median duration of response was not reached (95% CI = 30.9 months to not reached).
In approach 2, only baseline lesions with a measurable (≥ 1 cm maximum diameter) solid lesion were evaluated. On this approach, objective response was observed in 19 (76%, 95% CI = 55%–91%) of 25 patients, with complete response in 1 (4%). An additional 5 patients (20%) had stable disease. Median response duration was not reached (95% CI = 33.8 months to not reached).
Grade ≥ 3 adverse events occurred in 23 patients (46%). Grade 3 adverse events occurred in 19 (38%), most commonly anemia (12%), and grade 4 adverse events occurred in 2 patients (4%; retinal vein occlusion and embolism). Adverse events led to death in two patients (suicide and multiple toxicities), with neither death considered related to treatment.
The investigators concluded: “Belzutifan showed meaningful antitumour activity in VHL disease–associated CNS haemangioblastomas that was sustained for more than 3 years of treatment. These results continue to support belzutifan as a systemic treatment option for patients with VHL disease–related CNS haemangioblastomas.”
Othon Iliopoulos, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme, National Institutes of Health, and National Cancer Institute. For full disclosures of the study authors, visit www.thelancet.com.
