Advanced Renal Cell Carcinoma: Practical Sequencing Strategies Following First-Line Therapy

Dr. Monty Pal begins the discussion on treatment sequencing in advanced renal cell carcinoma (RCC) by emphasizing the importance of optimizing first-line therapy, noting that many patients may not receive multiple subsequent lines of treatment. He explains that treatment decisions should prioritize the greatest opportunity for durable clinical benefit rather than reserving therapies for later use. Dr. Pal outlines his approach to second-line treatment following progression on different frontline regimens, highlighting how prior therapy, patient fitness, treatment tolerability, and disease characteristics influence subsequent treatment selection. He discusses his use of lenvatinib plus everolimus for appropriate fit patients following progression on nivolumab and cabozantinib, alternative options for more frail individuals or those with intolerance to tyrosine kinase inhibitors, and the continued role of cabozantinib-based therapy after progression on other frontline immunotherapy combinations. Throughout the discussion, Dr. Pal reinforces the importance of individualized sequencing strategies to maximize long-term outcomes for patients with advanced renal cell carcinoma.