Cabozantinib and Novel Doublets in Advanced RCC
March 12, 2026
Key Points
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Lenvatinib plus belzutifan showed a trend toward improved overall survival (OS), but the benefit was not significant as of current interim analyses.
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Cabozantinib may still be preferred for many patients given its more favorable toxicity profile.
ASCO GU 2026 Data: Second-Line Treatment of Advanced RCC
At the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU 2026), Sumanta Pal, MD, FASCO, of City of Hope, and Nicholas Simon, MD, of MedStar Health, discussed the use of cabozantinib versus lenvatinib plus belzutifan in second-line treatment of patients with advanced RCC previously treated with anti–PD-1 or anti–PD-L1 therapy.
In the LITESPARK-011 trial, lenvatinib plus belzutifan showed superior PFS and ORR compared with cabozantinib, according to the late-breaking abstract presented at ASCO GU 2026. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 84.1% of the lenvatinib plus belzutifan arm versus 82.7% of the cabozantinib arm, and serious TEAEs occurred in 51.6% versus 43.9%, respectively. In the lenvatinib plus belzutifan arm, 15.4% of patients had any-grade hypoxia, and 11.9% had grade 3 or higher hypoxia. No patients in the cabozantinib arm had hypoxia.
Due to the priority of palliation and quality of life in the second-line setting, Dr. Pal said he would likely still use cabozantinib in the “vast majority” of patients given the more favorable toxicity profile. However, this approach could change if lenvatinib plus belzutifan showed a large OS benefit over cabozantinib in future survival analyses, he said.