A phase 1/2 clinical trial led by Roswell Park Comprehensive Cancer Center demonstrated that an alternating combination of pazopanib and bevacizumab extended survival in patients with treatment-naive metastatic clear-cell renal cell carcinoma. Evaluated across five U.S. centers, 51 patients achieved a median progression-free survival of 24.8 months and overall survival of 63.2 months, with favorable-risk patients reaching 76.9 months overall survival. The novel VEGF-targeting regimen delayed resistance, proved well tolerated, and offers an economical alternative to immunotherapy combinations.
Survival and efficacy outcomes
- ▪In the phase 2 trial, 51 evaluable patients achieved a median progression-free survival of 24.8 months and a median overall survival of 63.2 months after a median follow-up of 63.7 months.
- ▪Among 33 favorable-risk patients in the trial, the alternating bevacizumab and pazopanib regimen yielded a median progression-free survival of 28.5 months and a median overall survival of 76.9 months.
- ▪A phase 1/2 clinical trial published in The Lancet Oncology demonstrated that an alternating regimen of oral pazopanib and intravenous bevacizumab extended survival in treatment-naive metastatic clear-cell renal cell carcinoma patients.
- ▪Single-agent pazopanib in untreated metastatic clear-cell renal cell carcinoma yields a historical median progression-free survival of 9.2 months and overall survival of 28.4 to 29.3 months.
Safety and adverse events
- ▪The most common grade 3 to 4 adverse events in the trial were hypertension in 20 of 59 patients (34%), elevated alanine aminotransferase in 10 (17%), and elevated aspartate aminotransferase in 7 (12%).
- ▪Five of 59 patients (8%) discontinued the trial due to drug-related serious adverse events, and no treatment-related deaths were recorded.
Mechanism of action and resistance
- ▪Resistance to single-agent tyrosine kinase inhibitors in metastatic clear-cell renal cell carcinoma develops in part due to an unopposed rise in vascular endothelial growth factor (VEGF) ligand levels during treatment.
- ▪Alternating pazopanib with the monoclonal antibody bevacizumab binds and removes circulating VEGF ligands, delaying treatment resistance in patients with metastatic clear-cell renal cell carcinoma.
Clinical utility and affordability
- ▪The alternating VEGF-targeted regimen offers a treatment option for kidney cancer patients unable to receive immune checkpoint inhibitors due to autoimmune conditions, prior disease progression, or high drug costs.
- ▪The alternating pazopanib and bevacizumab regimen provides a lower-cost therapeutic option compared to standard immune checkpoint inhibitor combination therapies in metastatic clear-cell renal cell carcinoma.
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