Study: Combining Targeted Therapies Extends Kidney Cancer Survival
Trial Results for Bevacizumab and Pazopanib in Kidney Cancer
Combining the targeted therapies bevacizumab and pazopanib significantly extends progression-free and overall survival in patients with untreated metastatic clear cell renal cell carcinoma, according to phase 1/2 clinical trial results published in The Lancet Oncology. The study, led by Roswell Park Comprehensive Cancer Center, evaluated 51 treatment-naïve patients across five academic centers under clinical trial registration NCT01684397.
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Key Clinical Takeaways:
- Patients treated with the alternating combination regimen achieved a median progression-free survival of 24.8 months and a median overall survival of 63.2 months.
- The strongest survival benefit appeared in favorable-risk patients, who recorded a progression-free survival of 28.5 months and an overall survival of 76.9 months.
- High blood pressure and elevated liver enzymes emerged as the most common serious side effects during the trial.
Survival Outcomes Across Risk Categories
When pazopanib is administered alone as a first-line monotherapy for metastatic clear cell renal cell carcinoma, median progression-free survival reaches just 9.2 months, while overall survival spans from 28.4 to 29.3 months. By alternating pazopanib with bevacizumab, researchers observed a substantial expansion in longevity parameters across the 51 participants evaluated in the phase 2 portion of the trial after a median follow-up of 63.7 months. Among these participants, 33 individuals categorized as favorable risk per the guidelines of the International Metastatic RCC Database Consortium experienced the most pronounced gains.
While contemporary treatment paradigms for advanced renal cell carcinoma frequently rely on immunotherapy combined with a tyrosine kinase inhibitor, these standard regimens often fail to deliver a statistically significant improvement in overall survival specifically within favorable-risk patient populations. This dual-VEGF-blocking approach costs less than standard immunotherapy regimens.
Biological Mechanisms of Dual VEGF Inhibition
The researchers believe this is the first clinical trial in kidney cancer to demonstrate both safety and efficacy by combining two distinct agents that target vascular endothelial growth factor. This protein stimulates new blood vessel growth that supplies tumors with oxygen and nutrients. Multi-targeted tyrosine kinase inhibitors like pazopanib typically provoke rising VEGF ligand levels over successive treatment cycles, accelerating drug resistance. Bevacizumab, a monoclonal antibody, intervenes by binding directly to circulating VEGF and clearing it from the bloodstream.
The two-part clinical trial established optimal dosing schedules during its initial phase. Patients received 800 mg of pazopanib daily on days 1 through 28, combined with 10 mg/kg of bevacizumab administered on days 36 and 50 within a structured 10-week cycle. Saby George, professor of oncology in the Department of Medicine at Roswell Park and principal investigator of the study, noted that the alternating regimen delayed treatment resistance and proved reasonably well-tolerated, with high blood pressure and elevated liver enzymes identified as the primary serious adverse events.
Beyond its efficacy in untreated metastatic disease, investigators indicate that this therapeutic strategy holds potential utility for individuals who cannot tolerate immunotherapy agents, patients experiencing disease progression following adjuvant pembrolizumab, and populations residing in resource-limited countries. Rahul Parikh of the University of Kansas served as senior author on the publication. The investigator-initiated trial received sponsorship from Roswell Park in collaboration with Novartis, bringing a lower-cost, highly active regimen forward for a patient population in ongoing need of optimized first-line options.
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