- Published in The Lancet, results of the phase III LITESPARK-011 clinical trial point to the combination of belzutifan plus lenvatinib as a potential new standard of care for patients with advanced renal cancer whose disease has progressed on prior immunotherapy.
- Co-authored by Cristina Suárez, Head of VHIO’s Genitourinary (non-prostate), Central Nervous System Tumors (CNS), Sarcomas, and Tumors of Unknown Origin Group and Medical Oncologist at the Vall d’Hebron University Hospital, the findings show that the new combination reduced the risk of disease progression or death by 30% versus current cabozantinib monotherapy.
Published today in The Lancet, results of the international, open-label phase III LITESPARK-011 trial show that the belzutifan-lenvatinib combination improved disease control compared to standard of care with cabozantinib in patients with advanced clear-cell renal-cell carcinoma (ccRCC) with disease progression after prior treatment with immunotherapy.
In 2022, there were more than 430,000 new kidney cancer cases and over 15,000 deaths worldwide. The most common form of kidney cancer is ccRCC, which accounts for approximately four in five cases. About 20% of these patients present with metastasis when they are first diagnosed, and the disease will continue to spread in one-third of these cases even after surgery.
“Most patients with clear cell renal carcinoma receive immunotherapy first. However, for those patients who experience disease progression on or after immunotherapy, therapeutic options are limited and there is no clearly defined standard of care,” said Cristina Suárez, Medical Oncologist at the Vall d’Hebron University Hospital, Head of VHIO’s Genitourinary (non-prostate), Central Nervous System Tumors (CNS), Sarcomas, and Tumors of Unknown Origin Group, and co-author of the study published today in The Lancet.
“The most common treatment in this disease setting is cabozantinib, a tyrosine kinase inhibitor that blocks tumor blood vessel growth.”
Led by Robert J. Motzer at the Memorial Sloan Kettering Cancer Center, New York, LITESPARK-011 was designed to evaluate if the combination of belzutifan plus lenvatinib would control cancer growth better in patients with previously treated advanced ccRCC versus traditional monotherapy with cabozantinib.
Belzutifan works by inhibiting HIF-2α, a protein implicated in the growth and survival of most ccRCC tumors. Lenvatinib, a multikinase inhibitor, blocks the formation of new blood vessels that tumors need to survive and grow. By disrupting different biological pathways, this two-pronged treatment strategy aims to better control tumor growth.
The study enrolled 747 patients with advanced ccRCC with disease progression following treatment with immune checkpoint inhibitors (ICIs) and prior VEGFR-TKI, who were randomly assigned (1:1) to receive the belzutifan-lenvatinib combination or cabozantinib.
At a median follow-up of 29 months, the investigators observed that the investigational combination achieved better outcomes compared to cabozantinib alone. The findings showed that the cancer shrank or disappeared in 53% of patients in the belzutifan-lenvatinib group, versus 40% in the cabozantinib group. Median progression-free survival was 14.8 months with the combination treatment versus 10.7 months with cabozantinib, which represents a 30% reduction in the risk of disease progression or death.
While overall survival data showed a favorable trend for the combination of 34.9 months versus 27.6 months in the control group, statistical significance was not reached. Longer follow-up will be necessary to confirm the benefit.
“The results of the LITESPARK-011 study represent a significant advance because they demonstrate, for the first time, that a new combination of treatments can significantly improve disease control compared to current therapy in this patient population,” concluded Cristina Suárez.
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Reference
Prof. Robert J. Motzer, M.D.; Prof. Ray McDermott, M.D.; Prof. Se Hoon Park, M.D.; Mauricio Burotto, M.D.; Prof. Roberto Iacovelli, M.D., Ph.D.; Elena Verzoni, M.D.; Cristina Suárez, M.D., Ph.D.; Prof. Masatoshi Eto, M.D., Ph.D.; Hernan J. Cutuli, M.D.; Prof. Camillo Porta, M.D.; Ray Manneh Kopp, M.D.; Prof. Sylvie Rottey, M.D.; Guillermo de Velasco, M.D., Ph.D.; Begoña P. Valderrama, M.D.; Prof. Arun A. Azad, M.D., Ph.D.; Ugo De Giorgi, M.D., Ph.D.; Michel Pavic, M.D.; Piotr Tomczak, M.D., Ph.D.; Prof. Robert Figlin, M.D.; Hans M. Westgeest, M.D., Ph.D.; Annalisa Guida, M.D.; Prof. Andrea Necchi, M.D.; Fabio A. Schutz, M.D.; Britt B. M. Suelmann, M.D., Ph.D.; Prof. John B.A.G. Haanen, M.D.; Sammy Yuan, Ph.D.; Rodolfo F. Perini, M.D.; Ding Wang, M.D., Ph.D.; Daniel Y.C. Heng, M.D.; Manuela Schmidinger, M.D., en representación de los investigadores del estudio LITESPARK-011. Belzutifan plus lenvatinib versus cabozantinib in previously treated advanced renal-cell carcinoma (LITESPARK-011): a randomised, open-label, phase 3 trial. Lancet. 2026 Aug 12:S0140-6736(26)01089-5. doi: 10.1016/S0140-6736(26)01089-5. Online ahead of print.
