From the Guidelines
Renal cell carcinoma with brain metastases should be managed with a combination of local brain treatment and systemic therapy, prioritizing local therapy with radiotherapy and/or surgery for optimal intracranial disease control, as recommended by the most recent ASCO guideline 1.
Key Considerations
- The management of brain metastases in renal cell carcinoma (RCC) is crucial for improving patient outcomes, and local therapy should be the standard of care, with decision-making individualized based on the pattern of intracranial metastases 1.
- Systemic therapy options, such as tyrosine kinase inhibitors (TKIs) or immunotherapy, can be used in conjunction with local brain treatment, but their efficacy in controlling brain metastases is limited, with a median progression-free survival (PFS) of 5.6 months and overall survival (OS) of 9.2 months in a study of sunitinib in patients with untreated brain metastases 1.
- Stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) can be used for local brain treatment, depending on the number and location of brain metastases, with SRS preferred for limited brain metastases (1-4 lesions) and WBRT for multiple lesions.
- First-line systemic options may include the combination of pembrolizumab plus axitinib, or ipilimumab plus nivolumab, with single-agent TKIs like cabozantinib or sunitinib considered for patients with poor performance status.
Treatment Approach
- Local brain treatment with radiotherapy and/or surgery should be prioritized for optimal intracranial disease control, with systemic therapy used to manage systemic disease.
- Neurosurgical resection should be considered for large symptomatic lesions causing significant mass effect, and corticosteroids may be needed to control cerebral edema.
- Regular brain MRIs every 2-3 months are essential for monitoring response to treatment, with adjustments made as needed to optimize patient outcomes.
Evidence Base
- The recommended approach is based on the most recent ASCO guideline 1, which emphasizes the importance of local therapy in managing brain metastases in RCC, as well as the limited efficacy of systemic therapy in controlling intracranial disease.
- Additional evidence from studies of systemic therapy options, such as sunitinib and cabozantinib, supports the use of these agents in conjunction with local brain treatment, but highlights the need for individualized decision-making based on patient-specific factors 1.
From the FDA Drug Label
INDICATIONS AND USAGE Sunitinib malate capsules are a kinase inhibitor indicated for: ... (1.2) treatment of adult patients with advanced renal cell carcinoma (RCC).
14.1 Renal Cell Carcinoma The efficacy of pazopanib was evaluated in VEG105192, a randomized, double-blind, placebo-controlled, multicenter trial ( NCT00387764). Patients with locally advanced and/or metastatic RCC who had received either no prior therapy or one prior cytokine-based systemic therapy were randomized (2:1) to receive pazopanib 800 mg once daily or placebo once daily
Treatment of Renal Cell Carcinoma with Brain Metastases:
- Sunitinib 2 and pazopanib 3 are indicated for the treatment of advanced renal cell carcinoma (RCC).
- However, there is no direct information in the provided drug labels regarding the treatment of RCC with brain metastases.
- Therefore, no conclusion can be drawn about the efficacy or safety of these drugs in this specific patient population.
From the Research
Overview of Renal Cell Carcinoma with Brain Metastases
- Renal cell carcinoma (RCC) with brain metastases is a complex condition that requires a multimodal treatment approach 4, 5, 6.
- The incidence of brain metastases in patients with metastatic RCC has been reported to be around 13% 7.
- Tyrosine kinase inhibitors (TKIs) have been shown to improve overall survival (OS) in patients with RCC and brain metastases 4, 7.
Treatment Options for Brain Metastases
- Radiation therapy, including stereotactic radiosurgery and whole-brain radiotherapy, is a common treatment option for brain metastases 4, 5.
- Surgery may also be considered for patients with a single brain metastasis or for those with multiple metastases that are symptomatic 4, 6.
- Immunotherapy, including immune checkpoint inhibitors, has been shown to improve OS in patients with RCC and brain metastases 5, 8.
Role of Tyrosine Kinase Inhibitors
- TKIs have been shown to reduce the incidence of brain metastases in patients with metastatic RCC 7.
- TKIs may also improve OS in patients with RCC and brain metastases, particularly in those who have not previously received TKI therapy 4, 5.
- The combination of TKIs with immunotherapy may provide additional benefits in terms of OS and progression-free survival 8.
Challenges and Unmet Needs
- The optimal approach for the management of brain metastases from RCC remains unclear 6.
- Further research is needed to understand the tumor and immune biology of brain metastases in RCC, as well as the drivers of resistance to systemic treatment 6.
- An interdisciplinary consensus on the management of brain metastases in patients with RCC is necessary to improve patient care 6.