From the Guidelines
Treatment for metastatic renal cell carcinoma (mRCC) should prioritize first-line therapy with immune checkpoint inhibitors like nivolumab (240 mg IV every 2 weeks) plus ipilimumab (1 mg/kg IV every 3 weeks for 4 doses), or a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) monotherapy, based on the most recent and highest quality study 1.
First-Line Treatment Options
- Immune checkpoint inhibitors: nivolumab plus ipilimumab, or pembrolizumab plus axitinib
- VEGFR TKI monotherapy: cabozantinib, sunitinib, or pazopanib
Second-Line Treatment Options
- For patients who received VEGFR TKI monotherapy as first-line treatment: nivolumab or cabozantinib
- For patients who received combination immunotherapy as first-line treatment: VEGFR TKI monotherapy
- For patients who received VEGFR TKI with an immune checkpoint inhibitor as first-line treatment: an alternative VEGFR TKI as a single agent
Special Considerations
- Patients on immunotherapy who experience limited disease progression may be offered local therapy (radiation, thermal ablation, and excision) and continuation of immunotherapy 1
- Surgical options like cytoreductive nephrectomy may benefit selected patients with good performance status
- Metastasectomy can be considered for isolated metastases
Side Effect Management
- Monitoring for immune-related adverse events with immunotherapy
- Monitoring for hypertension, diarrhea, and hand-foot syndrome with TKIs The treatment selection should be based on patient risk category, performance status, and comorbidities, as well as the consideration of the most recent and highest quality evidence 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). INDICATIONS AND USAGE CABOMETYX is a kinase inhibitor indicated for the treatment of patients with advanced renal cell carcinoma (RCC) 1.7 Advanced Renal Cell Carcinoma • OPDIVO, in combination with ipilimumab, is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced RCC. • OPDIVO, in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced RCC
Treatment options for metastatic renal cell carcinoma include:
- Sunitinib malate capsules 2
- Cabozantinib (CABOMETYX) 3
- Nivolumab (OPDIVO) in combination with ipilimumab or cabozantinib 4 Key points:
- Sunitinib and cabozantinib are kinase inhibitors
- Nivolumab is an immune checkpoint inhibitor
- Combination therapy with nivolumab and ipilimumab or cabozantinib is indicated for first-line treatment of advanced RCC
From the Research
Treatment Options for Metastatic Renal Cell Carcinoma
- Nivolumab plus ipilimumab has shown efficacy benefits over sunitinib in patients with intermediate/poor-risk metastatic renal cell carcinoma, with a median overall survival of 48.6 months versus 14.2 months 5.
- A study comparing first-line ipilimumab with nivolumab versus immune checkpoint inhibitors with tyrosine kinase inhibitors found no significant difference in real-world overall survival, but a shorter time to next therapy with ipilimumab plus nivolumab 6.
- Nivolumab plus ipilimumab has been shown to produce objective responses in patients with advanced renal-cell carcinoma, with an overall survival rate of 75% at 18 months, compared to 60% with sunitinib 7.
First-Line and Second-Line Treatments
- Sunitinib and pazopanib are considered treatment options for patients with favorable or intermediate-risk features and clear cell histology, while temsirolimus is the only option supported by level 1 evidence for patients with poor-risk features 8.
- A network meta-analysis found that cabozantinib, avelumab plus axitinib, and pembrolizumab plus axitinib were superior to other agents for progression-free survival, while pembrolizumab plus axitinib appeared superior for overall survival 9.
Efficacy and Safety
- Nivolumab plus ipilimumab has been shown to have a higher objective response rate and complete response rate compared to sunitinib, with a median duration of response that was longer 5.
- Treatment-related adverse events were common with both nivolumab plus ipilimumab and sunitinib, but grade 3 or 4 events were more frequent with sunitinib 7.