Two international phase III trials-LITESPARK-022 and LITESPARK-011-demonstrate the potential benefits of the HIF-2α inhibitor belzutifan for patients with clear cell renal cell carcinoma. When combined with the PD-1 inhibitor pembrolizumab as an adjuvant treatment, it reduced the risk of disease recurrence by 28% and prolonged disease-free survival over pembrolizumab alone. For patients whose disease returned following immunotherapy, belzutifan and the VEGFR inhibitor lenvatinib bested the VEGFR inhibitor cabozantinib in overall response, progression-free survival, and duration of response.
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