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Belzutifan improves outcomes over everolimus in patients with previously treated, advanced clear cell renal cell carcinoma (RCC), according to results from the LITESPARK-005 study presented at the ESMO Congress 2023.
Belzutifan improved progression-free survival (PFS) as well as the rate and duration of response in this study.
LITESPARK-005 is the first positive phase 3 study in patients with advanced RCC whose disease progressed on immune checkpoint inhibitors and VEGFR tyrosine kinase inhibitors (TKIs), said study presenter Laurence Albiges, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
LITESPARK-005 (ClinicalTrials.gov Identifier: NCT04195750) included 374 patients with unresectable, locally advanced or metastatic clear cell RCC. The patients had received 1-3 prior lines of therapy including at least 1 anti-PD-(L)1 antibody and at least 1 VEGFR-TKI.
The patients were randomly assigned to receive belzutifan at 120 mg daily (n=374) or everolimus at 10 mg daily (n=372). At last follow-up, 22.6% of patients in the belzutifan arm and 5.0% in the everolimus arm were still on study treatment.
The primary endpoints of this study are PFS by blinded independent central review (BICR) and overall survival (OS). Dr Albiges reported data from the first interim analysis, with a median follow-up of 18.4 months, and the second interim analysis, with a median follow-up of 25.7 months.
At both time points, the median PFS per BICR was 5.6 months in both treatment arms. However, there was a statistically significant improvement in PFS with belzutifan at the first interim analysis (hazard ratio [HR], 0.75; 95% CI, 0.63-0.90; P <.001) and the second interim analysis (HR, 0.74; 95% CI, 0.63-0.88).
The 12-month PFS rate was 33.7% with belzutifan and 17.6% with everolimus. The 18-month PFS rate was 22.5% and 9.0%, respectively.
At the first interim analysis, the median OS was 21.0 months with belzutifan and 17.2 months with everolimus (HR, 0.87; 95% CI, 0.71-1.07; P =.096). At the second interim analysis, the median OS was 21.4 months with belzutifan and 18.1 months with everolimus (HR, 0.88; 95% CI, 0.73-1.07; P =.099).
The 12-month OS rate was 67.9% with belzutifan and 65.8% with everolimus. The 18-month OS rate was 55.2% and 50.6%, respectively.
At the first interim analysis, the overall response rate (ORR) was 21.9% with belzutifan and 3.5% with everolimus (P <.00001). At the second interim analysis, the ORR was 22.7% and 3.5%, respectively. The median duration of response was 19.5 months and 13.7 months, respectively.
The rate of grade 3-5 treatment-related adverse events (AEs) was 38.7% in the belzutifan arm and 39.4% in the everolimus arm. There was 1 fatal treatment-related AE in the belzutifan arm (multiple organ dysfunction syndrome) and 2 in the everolimus arm (sepsis and acute kidney injury).
The most common AEs of any grade and any cause in the belzutifan arm were anemia (82.8%), fatigue (31.5%), and nausea (18.0%). The most common AEs of any grade and any cause in the everolimus arm were anemia (56.7%), stomatitis (37.8%), and fatigue (25.3%).
Disclosures: This research was supported by Merck Sharp & Dohme LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Albiges L, Rini BI, Peltola K, et al. Belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC): Randomized open-label phase III LITESPARK-005 study. Presented at ESMO Congress 2023. Oct. 20-24, 2023. Madrid, Spain. Abstract LBA88.
This article originally appeared on Cancer Therapy Advisor
