Pragmatic trials in renal cell carcinoma
Therapeutic options for Renal Cell Carcinoma (RCC) are rapidly advancing. Systemic immune-oncology (IO) treatments, including immune checkpoint inhibitor (ICI) combination therapy and ICI with vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKIs), have shown substantial overall survival advantages. Data comparing first-line treatments for advanced RCC is limited, and second- and third-line therapies are frequently determined by approvals prior to current therapies. Pragmatic clinical trials (PCTs) are designed to inform a clinical decision by implementing evidence in a real-world setting. PCTs have increasing relevancy in oncology and offer advantages including generalizability, ease of trial execution, and can assist in evaluating whether therapies exhibit equivalent efficacy in clinical practice. Several PCTs have provided insight into metastatic RCC (mRCC) management. COMPARZ and PICSES trials compared pazopanib to sunitinib for mRCC patients and offered new insights into tolerability and patient preference. The MaRCC Registry yielded real-world data on treatment patterns and physician decision-making. The CARMENA trial demonstrated non-inferiority of sunitinib alone versus nephrectomy followed by sunitinib, while the STAR trial explored standard continuous versus intermittent VEGF-TKI therapy. Ongoing PCTs include the PROBE trial, ODYSSEY RCC, and CARE1 trials. Future opportunities for PCTs include comparing second-line treatment regimens for mRCC, examining differences in clinical responses by gender or age, the use of consolidative tumor-directed therapy in oligometastatic disease or for debulking metastases, and the impact of lifestyle variances on management. PCTs are needed to fill knowledge gaps and address patient-centered priorities that can inform our practices and improve quality care for patients with mRCC.
