Is cabozantinib (tyrosine kinase inhibitor) alone better than cabozantinib plus embolization for oligometastatic renal cell carcinoma (RCC) patients who have had clinical and radiological progression on nivolumab (monoclonal antibody) and ipilimumab (monoclonal antibody)?

From the Guidelines

Cabozantinib alone is the preferred treatment for oligometastatic renal cell carcinoma patients who have had clinical and radiological progression on nivolumab and ipilimumab, due to its established efficacy and lack of robust comparative data supporting the addition of embolization. For these patients who have failed immunotherapy, cabozantinib monotherapy (typically 60mg daily, with dose reductions to 40mg or 20mg as needed for side effects) is a standard approach with established efficacy, as seen in the CONTACT-03 study 1. The impressive ORR (40.9%) and median PFS (10.8 months) observed in the control arm of CONTACT-03 make second-line cabozantinib monotherapy an attractive approach.

The addition of embolization to cabozantinib therapy represents a combined locoregional and systemic approach that has theoretical benefits but lacks robust comparative data in this specific post-immunotherapy setting. While embolization can provide local control of specific lesions by cutting off their blood supply, potentially enhancing the systemic effects of cabozantinib, this combination approach may increase overall treatment burden and potential complications.

Some key points to consider when making treatment decisions include:

• The patient's performance status
• Location and number of metastases
• Prior treatment response
• Goals of care A multidisciplinary tumor board discussion involving medical oncology, interventional radiology, and surgical oncology would be valuable for determining the optimal approach for each patient, as seen in the management of metastatic clear cell renal cell carcinoma guideline 1.

In terms of the evidence, the phase III CONTACT-03 study evaluated atezolizumab plus cabozantinib versus cabozantinib alone in patients who had disease progression with ICI therapy, and found that the addition of ICI therapy did not improve OS or PFS, but increased toxicity 1. Similarly, the phase III LITESPARK-005 study of belzutifan versus everolimus in previously treated ccRCC included patients who had received one previous line of therapy, and found that belzutifan is an option for second-line therapy after progression on VEGFRePD-1-targeted combination therapy, but with a weaker level of recommendation than in third-line treatment 1.

Overall, the current evidence supports the use of cabozantinib alone as the preferred treatment for oligometastatic renal cell carcinoma patients who have had clinical and radiological progression on nivolumab and ipilimumab.

From the Research

Comparison of Cabozantinib Alone and Cabozantinib Plus Embolization

• There are no direct studies comparing cabozantinib alone to cabozantinib plus embolization for oligometastatic renal cell carcinoma (RCC) patients who have had clinical and radiological progression on nivolumab and ipilimumab 2, 3, 4, 5, 6.
• However, studies suggest that local therapies such as stereotactic body radiation therapy (SBRT) and metastasectomy can be effective in managing oligometastatic RCC, allowing for a delay in systemic therapy 2, 3, 5, 6.
• The use of tyrosine kinase inhibitors (TKIs) like cabozantinib as second-line therapy in mRCC patients has shown promise, with some studies suggesting improved progression-free survival (PFS) and overall survival (OS) in certain patient subpopulations 4.
• Focal therapy options, including resection, SBRT, and thermal ablation, may be considered for oligometastatic and oligoprogressive RCC, but patient selection and choice of treatment technique are controversial due to limited data 5.
• Multidisciplinary management of oligometastatic RCC, including cytoreductive nephrectomy, metastasectomy, SBRT, and systemic therapy, is recommended, with active surveillance considered before initiating systemic therapy 6.

Considerations for Treatment

• The decision to use cabozantinib alone or in combination with embolization should be based on individual patient characteristics, tumor biology, and prior treatment history 4.
• Further research is needed to determine the optimal treatment approach for oligometastatic RCC patients who have progressed on nivolumab and ipilimumab, including the potential role of embolization in combination with cabozantinib 3, 5, 6.