Second-Line Strategy After IO and TKI in Advanced Renal Cell Carcinoma

In this case-based segment on advanced renal cell carcinoma, Dr. Ornstein presents a patient who progresses after frontline immunotherapy plus VEGF receptor targeted therapy, with prior tolerability challenges including hand-foot syndrome and diarrhea. He highlights the expanding range of second-line options, including HIF-2α inhibitors.

Dr. Singer discusses his approach, emphasizing that treatment selection depends on both disease tempo and prior toxicity. For patients experiencing significant side effects from prior therapy, he considers better tolerated VEGF receptor targeted therapies such as tivozanib or axitinib. However, in cases of more aggressive or rapidly progressing disease, he favors more potent options such as cabozantinib despite potential toxicity. He also discusses the role of belzutifan monotherapy, noting its potential for durable responses in selected patients, while acknowledging the risk of primary progression. The discussion highlights a nuanced, patient-centered approach that balances efficacy, tolerability, and clinical urgency in second-line decision-making for advanced renal cell carcinoma.