- Results of the phase III LITESPARK-005 clinical trial show that treatment with belzutifan versus everolimus significantly improves progression-free survival in patients with advanced clear cell renal cell carcinoma.
- Belzutifan is the first oral inhibitor of hypoxia-inducible factor 2α (HIF-2α) approved in the United States for cancers associated with von-Hippel-Lindau Syndrome, a rare genetic disease that can cause tumors in different parts of the body, including the kidneys.
- Findings of this study, co-authored by Cristina Suárez, Medical Oncologist at Vall d’Hebron and Clinical Investigator at VHIO, have published in The New England Journal of Medicine.
Accounting for 2-3% of malignant tumors in adults, renal cell carcinoma (RCC), also known as renal cell adenocarcinoma, is a rare disease originating in the lining of kidney tubules. Clear cell RCC (ccRCC) is the most common type of kidney cancer, representing almost 80% of all cases.
“If detected early, most people with kidney cancer can be cured with surgery. However, the prognosis of metastatic clear cell renal cell carcinoma is poor and identifying new therapies to improve outcomes for patients who are refractory to immunotherapy and VEGF-targeted therapies represents and unmet clinical need,” said Cristina Suárez, Medical Oncologist at the Vall d’Hebron University Hospital, Senior Clinical Investigator of VHIO’s Genitourinary, Central Nervous System Tumors (CNS) and Sarcoma Group, and co-author of this present study published in The New England Journal of Medicine.
Hypoxia is a common feature of most solid tumors, rendering them more resistant to therapy. Belzutifan is a first-in-class oral inhibitor of hypoxia-inducible factor 2α (HIF-2α) approved in the United States for the treatment of several tumor types associated with von-Hippel-Lindau Syndrome including renal cancer and neuroendocrine pancreatic tumors, among others.
The phase III LITESPARK-005 trial was designed to evaluate belzutifan versus targeted therapy with everolimus in 746 patients with advanced clear cell renal cell carcinoma who received prior treatment with immunotherapy and VEGF-targeted therapies, results of which were initially presented as late-breaking data at the ESMO Congress 2023, 20-24 October in Madrid.
In patients treated with belzutifan, the investigators observed a 25% delay in the time to disease progression compared with those patients who received everolimus, with an overall response rate of 21.9% versus 3.5%, respectively. The safety profile of belzutifan was consistent with prior reports, and the most frequent adverse events were anemia and fatigue. Health-related quality of life was maintained for a longer duration in patients receiving belzutifan.
“Upon evaluation by the different regulatory authorities and healthcare reimbursement systems, our data support belzutifan as a new treatment strategy based on HIF-2α blockade for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy and anti-VEGF therapy,” concluded Suárez.
Reference
Toni K. Choueiri, M.D.; Thomas Powles, M.D.; Katriina Peltola, M.D., Ph.D.; Guillermo de Velasco, M.D., Ph.D.; Mauricio Burotto, M.D.; Cristina Suárez, M.D., Ph.D.; Pooja Ghatalia, M.D.; Roberto Iacovelli, M.D., Ph.D.; Elaine T. Lam, M.D.; Elena Verzoni, M.D.; Mahmut Gumus, M.D.; Walter M. Stadler, M.D.; Christian Kollmannsberger, M.D.; Bohuslav Melichar, M.D.; Balaji Venugopal, M.D.; Marine Gross-Goupil, M.D., Ph.D.; Alexandr Poprach, M.D.; Maria De Santis, M.D.19; Fabio A. Schutz, M.D.; Se Hoon Park, M.D.; Dmitry A. Nosov, M.D.; Camillo Porta, M.D.; Jae Lyun Lee, M.D, Ph.D.; Xavier Garcia-del-Muro, M.D., Ph.D.; Elisa Biscaldi, M.D.; Ray Manneh Kopp, M.D.; Mototsugu Oya, M.D.; Li He, Ph.D.; Aobo Wang, Ph.D.; Rodolfo F. Perini, M.D.; Donna Vickery, M.D.; Laurence Albiges, M.D.; Brian Rini, M.D., on behalf of the LITESPARK-005 Investigators. Belzutifan Versus Everolimus for Advanced Renal-Cell Carcinoma. NEJM (2024), DOI: 10.1056/NEJMoa2313906
