Cabozantinib for Second-Line Treatment of Advanced or Metastatic Renal Cell Carcinoma

What Is the Issue? Immune checkpoint inhibitor–based therapies, especially dual immune checkpoint inhibitor regimens, are now frequently used as initial treatments for advanced or metastatic renal cell carcinoma (RCC). Cabozantinib has shown promise in RCC; however, cabozantinib is currently funded in the second-line setting for adult patients with advanced or metastatic RCC who have previously received other vascular endothelial growth factor (VEGF)-targeted therapy, limiting its availability in some second-line scenarios. There is a need to understand the clinical effectiveness of cabozantinib when used after the failure of first-line immune checkpoint inhibitor (ICI) regimens. What Did We Do? To inform decisions about the use of cabozantinib for adults with advanced or metastatic RCC who have previously received ICIs in the first line, we sought to identify and summarize related evidence regarding the clinical effectiveness of second-line treatment with cabozantinib compared with sunitinib, axitinib, and pazopanib. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2020. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included publication, and summarized the findings. What Did We Find? One systematic review that included 2 small retrospective observational studies provided evidence for the research question. Limited retrospective evidence suggests that second-line treatment with cabozantinib may be associated with numerically longer progression-free survival (PFS) compared to sunitinib and axitinib, but shorter PFS compared to pazopanib. Cabozantinib may also have a potentially higher objective response rate (ORR) compared to sunitinib, axitinib, and pazopanib. One small retrospective study indicated that cabozantinib had the numerically lowest rate of treatment discontinuation due to toxicity compared to sunitinib, pazopanib, and axitinib. No studies reporting adverse event rates, overall survival (OS), or quality of life were identified. What Does It Mean? Decision-makers should consider the limited quantity and quality of the current evidence available for this patient population. Due to very low confidence in the body of evidence (small sample size, retrospective design, lack of statistical analyses), decision-makers choosing among second-line interventions cabozantinib, sunitinib, axitinib, and pazopanib should consider factors such as clinician expertise and/or patients’ values and preferences. Higher-quality research (with larger sample sizes, appropriate statistical tests, and transparent reporting) is needed to better inform decision-making, such as robust clinical trials or well-planned prospective observational studies focusing on second-line therapy with tyrosine kinase inhibitors (TKIs) such as cabozantinib.