In extended follow-up of the phase II LITESPARK-004 trial reported in The Lancet Oncology, Srinivasan et al found that use of the hypoxia-inducible factor-2α inhibitor belzutifan was associated with maintained benefit in patients with von Hippel–Lindau disease–associated renal cell carcinoma.
The initial report from the trial supported approval of belzutifan in this setting.
Study Details
In the trial, 61 patients from sites in Denmark, France, the United Kingdom, and the United States enrolled between May 2018 and March 2019 and received belzutifan at 120 mg once-daily until progression or unacceptable toxicity. The primary endpoint was the proportion of patients with objective response on independent review committee assessment. The current report provides outcomes after median follow-up of 49.9 months (interquartile range = 48.9–52.2 months).
Key Findings
Objective response was observed in 41 (67%, 95% confidence interval [CI] = 54%–79%) of 61 patients, with complete response in 7 (11%). Median duration of response was not reached (95% CI = 41.3 months to not reached); 71.5% of responders had ongoing response at the last measurement at 42 months.
Median progression-free survival was 49.8 months (95% CI = 49.8 months to not reached), with a 42-month rate of 79%.
Overall, grade 3 treatment-related adverse events were observed in 18% of patients, most commonly anemia (11%) and fatigue (5%); no treatment-related grade 4 or 5 adverse events were observed. Serious treatment-related adverse events were observed in 7% of patients.
The investigators concluded: “Updated results support the use of belzutifan as systemic treatment for von Hippel-Lindau disease-associated renal cell carcinoma.”
Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co, and others. For full disclosures of all study authors, visit thelancet.com/journals/lanconc.
