First-Line Treatment Selection
Panelists discuss how treatment selection for a typical intermediate-risk patient with clear cell renal cell carcinoma (RCC) involves choosing between ipilimumab plus nivolumab for long-term durable responses in nonsymptomatic patients and immunotherapy-tyrosine kinase inhibitor (IO-TKI) combinations for those requiring rapid disease control or cytoreduction.
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Treatment selection for first-line clear cell RCC requires individualized assessment balancing efficacy, tolerability, and patient-specific factors. The expert panel discusses a representative case: a 62-year-old man with intermediate-risk disease, an 8 cm primary tumor, and multiple pulmonary nodules. All panelists favor ipilimumab plus nivolumab for this patient, citing adequate time for immune response development, noncritical disease burden, and potential for durable long-term control. The decision hinges on disease tempo rather than strict risk categorization, with asymptomatic patients having time to achieve the delayed but durable benefits of dual immunotherapy.
Critical factors influencing regimen choice include disease burden assessment, symptom severity, performance status, and comorbidity profile. Visceral crisis or rapidly progressive disease favors IO-TKI combinations for immediate disease control, while patients with stable, asymptomatic disease benefit from ipilimumab-nivolumab's superior long-term outcomes. Specific disease characteristics guide selection: Sarcomatoid histology strongly favors ipilimumab plus nivolumab due to its exceptional response rates; bone-dominant disease suggests cabozantinib combinations; and brain metastases may benefit from cabozantinib's central nervous system (CNS) penetration.
Patient counseling emphasizes the distinct toxicity profiles: immune-related adverse events with ipilimumab plus nivolumab requiring steroid management vs chronic TKI-related adverse effects with IO-TKI combinations. The panel discusses pseudoprogression management, generally allowing one additional scan for stable patients before declaring resistance. Treatment familiarity influences community practice patterns, with pembrolizumab-axitinib remaining popular despite newer options. The experts emphasize developing expertise with specific regimens rather than frequently switching between options, enabling optimal toxicity management and patient counseling.
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