Second-Line Treatment Decision-Making in Advanced Renal Cell Carcinoma

In this segment on advanced renal cell carcinoma, Dr. Ornstein transitions the discussion to the second-line setting, noting that most patients will eventually experience disease progression and require additional therapy. He highlights that treatment goals evolve in the refractory setting, where achieving disease control becomes the primary objective rather than long-term durable remission.

Dr. Singer outlines his clinical framework for second-line decision-making, emphasizing two key factors: the rate of disease progression and tolerability of prior therapy. He notes that re-challenging with PD-1–based therapy is generally not supported by current evidence, shifting the focus toward sequencing VEGF receptor targeted therapies. He discusses available options, including monotherapy and combination approaches such as lenvatinib with everolimus, as well as emerging strategies involving HIF-2α inhibitors. Dr. Singer emphasizes tailoring treatment intensity based on clinical urgency, balancing more potent but less tolerable options with better tolerated regimens depending on patient condition.