From the Guidelines
Cabozantinib alone is more effective than cabozantinib plus pembrolizumab in the treatment of oligometastatic renal cell carcinoma (RCC) in MSKCC intermediate-risk patients who have had clinical and radiological progression on ipilimumab plus nivolumab. The phase III CONTACT-03 study 1 evaluated atezolizumab plus cabozantinib versus cabozantinib alone in patients who had disease progression with ICI therapy and found that the combination therapy did not demonstrate improvements in either overall survival (OS) or progression-free survival (PFS) compared to cabozantinib alone. In fact, the study reported increased toxicity with the combination therapy, with serious adverse events occurring in 48% of patients receiving atezolizumab plus cabozantinib and 33% of patients receiving cabozantinib alone.
The impressive objective response rate (40.9%) and median PFS (10.8 months) observed in the control arm of CONTACT-03 make second-line cabozantinib monotherapy an attractive approach 1. Similarly, the phase III CANTATA study reported an objective response rate of 28% and a median PFS of 9.3 months in the cabozantinib control arm 1. These results suggest that cabozantinib alone is a preferred second-line VEGFR TKI therapy, especially in patients who have received prior ICI therapy.
In contrast, the COSMIC 313 study 1 evaluated the combination of cabozantinib, nivolumab, and ipilimumab in treatment-naïve patients with intermediate or poor prognostic risk metastatic ccRCC, but this study does not provide direct evidence for the treatment of patients who have progressed on ipilimumab plus nivolumab. Therefore, based on the most recent and highest quality study, cabozantinib alone is the recommended treatment for oligometastatic RCC in MSKCC intermediate-risk patients who have had clinical and radiological progression on ipilimumab plus nivolumab.
Key points to consider when treating these patients with cabozantinib alone include:
- Starting dose: 40mg orally daily
- Dose adjustments: may be needed based on tolerability, with cabozantinib potentially reduced to 20mg daily if side effects occur
- Treatment duration: typically continues until disease progression or unacceptable toxicity
- Imaging assessments: every 8-12 weeks to monitor response to treatment.
From the Research
Treatment Options for Oligometastatic RCC
The treatment of oligometastatic renal cell carcinoma (RCC) in Memorial Sloan Kettering Cancer Center (MSKCC) intermediate-risk patients who have progressed on ipilimumab plus nivolumab is a complex issue.
- The effectiveness of cabozantinib alone versus cabozantinib plus pembrolizumab in this setting is not directly addressed in the provided studies.
- However, studies have compared the efficacy of nivolumab and cabozantinib in patients with metastatic RCC, including those with intermediate-risk disease 2, 3.
- One study found that nivolumab and cabozantinib resulted in similar overall survival (OS) and time to treatment failure (TTF) in patients with metastatic RCC who had received prior therapy targeted to the vascular endothelial growth factor receptor (VEGFR) 3.
- Another study found that cabozantinib was associated with a longer progression-free survival (PFS) than nivolumab in patients with clear cell histology and good risk features 2.
Considerations for Treatment Choice
When considering the treatment of oligometastatic RCC in MSKCC intermediate-risk patients who have progressed on ipilimumab plus nivolumab, several factors should be taken into account.
- The patient's overall health and performance status should be considered, as well as the presence of any comorbidities or toxicities from prior therapies.
- The potential benefits and risks of each treatment option, including cabozantinib alone and cabozantinib plus pembrolizumab, should be carefully weighed.
- The results of studies comparing the efficacy of different treatment options in similar patient populations should be considered, although it is noted that the specific comparison of cabozantinib alone versus cabozantinib plus pembrolizumab in this setting is not directly addressed in the provided studies 4, 5, 6.