Patient Factors Guiding Frontline Regimen Selection in Advanced RCC

Selecting first-line therapy for advanced clear cell renal cell carcinoma (RCC) increasingly starts with a choice between dual immunotherapy and an immunotherapy plus tyrosine kinase inhibitor (TKI) combination. The panel explains how risk classification, symptom burden, and disease tempo inform that decision. Faculty describe an “eyeball test” for patients with heavy bone or pulmonary disease. They note that the lower rate of primary progression with immunotherapy-TKI regimens makes these the preferred approach when rapid disease control is essential. The conversation then turns to cabozantinib plus nivolumab, including its durable benefit in long-term pivotal trial follow-up and cabozantinib’s consistent activity in bone metastases, particularly when spinal involvement raises concern for cord compromise. The panel also reviews the attenuated cabozantinib dose used in the frontline combination. Faculty explain how they counsel patients that dose reductions are expected, reflect adequate drug exposure, and do not signal treatment failure.