Positive Trials for Belzutifan in Earlier Treatment Lines for RCC

Michael Serzan, MD Dana-Farber Cancer Institute | Toni Choueiri, MD Dana-Farber Cancer Institute

March 16, 2026

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Key Points

  • In the LITESPARK-011 trial, belzutifan plus lenvatinib improved outcomes compared with cabozantinib in patients with advanced renal cell carcinoma (RCC) after targeted therapy against PD-1 or PD-L1.

  • Adjuvant belzutifan plus pembrolizumab improved disease-free survival compared with pembrolizumab alone for patients with clear cell RCC in the LITESPARK-022 trial.

  • Utilizing belzutifan in any treatment setting requires proactive management of distinct side effects, including anemia and hypoxia.

ASCO GU 2026 Data for Belzutifan in RCC

At the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU 2026), Toni Choueiri, MD, and Michael Serzan, MD, both from Dana-Farber Cancer Institute, discussed new data on belzutifan, an oral hypoxia-inducible factor 2 alpha inhibitor, across different lines of therapy for RCC. Belzutifan was previously approved for advanced RCC after prior PD-1 or PD-L1 inhibitor and VEGF tyrosine kinase inhibitor (TKI) therapy. AT ASCO GU 2026, authors presented data on belzutifan combinations in earlier treatment settings.

The phase 3 LITESPARK-011 trial showed belzutifan plus lenvatinib improved progression-free survival (PFS) and objective response rate (ORR) compared with cabozantinib in patients with advanced RCC who progressed after anti–PD-1 or anti–PD-L1 therapy in first-line, second-line, or adjuvant treatment settings. The phase 3 LITESPARK-022 trial showed that adjuvant belzutifan plus pembrolizumab improved disease-free survival compared with pembrolizumab alone in high-risk clear cell RCC after nephrectomy. “Belzutifan is moving very rapidly. I don’t think I’ve seen in kidney cancer a drug move so rapidly from a refractory setting to an adjuvant setting,” said Dr. Choueiri.

For community medical oncologists, Dr. Choueiri noted that belzutifan has a very different side effect profile compared with contemporary TKI agents. Specifically, anemia and hypoxia are important side effects to monitor for and proactively manage. For anemia, oncologists should check iron, B12, and folate levels regularly and use supportive treatments like erythropoiesis-stimulating agents or transfusions as needed. The rate of hypoxia with belzutifan is lower, around 5% to 15%, depending on the patient population. However, oncologists still need to proactively monitor blood oxygen saturation and provide supplemental oxygen if necessary.