TOPLINE:
At 18 months, 24% of participants on belzutifan were alive and progression free, compared with 8.3% on everolimus.
METHODOLOGY:
- The phase 3, multicenter, open-label, randomized, active-controlled LITESPARK-005 trial was conducted at 147 sites in six regions.
- The trial aimed to compare the efficacy and safety of belzutifan with everolimus in 746 participants with advanced clear cell renal cell carcinoma who had disease progression after receiving immune checkpoint and antiangiogenic therapies.
- Patients were randomly assigned to receive either 120 mg of belzutifan or 10 mg of everolimus orally once daily and were followed for a median of 18.4 months at the first interim analysis and of 25.7 months at the second interim analysis.
- The dual primary endpoints were progression-free survival and overall survival, with the key secondary endpoint having been a confirmed objective response, defined as a complete or partial response.
- Dose modifications were allowed to manage adverse events, with belzutifan doses reduced to 80 mg and then to 40 mg daily if needed.
TAKEAWAY:
- Belzutifan showed a significant benefit over everolimus in progression-free survival, with 24% of participants on belzutifan alive and progression free at 18 months, compared with 8.3% on everolimus (P = .002).
- The objective response rate was significantly higher in the belzutifan group (21.9%) compared with the everolimus group (3.5%) (P < .001).
- The median overall survival was 21.4 months for belzutifan and 18.1 months for everolimus, with a hazard ratio for death of 0.88 (95% CI, 0.73-1.07; P = .20).
- Grade 3 or higher adverse events occurred in 61.8% of participants in the belzutifan group and in 62.5% in the everolimus group, with adverse events leading to treatment discontinuation in 5.9% and 14.7% of participants, respectively.
IN PRACTICE:
“The LITESPARK-005 trial introduced [hypoxia-Inducible factor 2 alpha] inhibition as an active therapeutic mechanism and established belzutifan as a treatment option in patients with advanced renal-cell carcinoma after both immune checkpoint and antiangiogenic therapies,” the authors wrote.
SOURCE:
Corresponding author Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, was one of four authors who contributed equally to the article, which was published on August 21 in The New England Journal of Medicine.
LIMITATIONS:
The study’s limitations include the open-label design, which may introduce bias. The trial did not include a placebo group, and the follow-up period may not be sufficient to capture long-term outcomes. In addition, the study population was heavily pretreated, which may limit the generalizability of the findings to broader patient populations.
DISCLOSURES:
Dr. Choueiri disclosed receiving consultancy fees from Merck, the sponsor of the study, and other pharmaceutical companies. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.