A novel treatment regimen combining pazopanib (Votrient) and bevacizumab (Avastin) has shown promising results in extending survival for patients with advanced kidney cancer. The phase 2 clinical trial, conducted at Roswell Park Comprehensive Cancer Center, demonstrated a significant improvement in progression-free survival compared to historical data with pazopanib alone.
The study involved 51 patients with treatment-naive metastatic clear cell renal cell carcinoma (ccRCC). Patients received pazopanib at 800 mg daily for 28 days, followed by bevacizumab at 10 mg/kg on days 36 and 50 of a 10-week cycle. This alternating regimen was designed to overcome potential resistance mechanisms associated with VEGF signaling.
Progression-Free Survival Doubled
The results, presented at the European Society for Medical Oncology (ESMO) Congress, revealed a median progression-free survival (PFS) of 22.1 months (95% CI, 15.9-27.4) with the combination therapy. This is more than double the 11.1 months observed in previous trials that led to the FDA approval of pazopanib for advanced RCC. The study was designed to detect a clinical benefit rate (CBR) of 60% vs 45%.
Clinical Benefit and Safety
The trial met its primary endpoint, with 40 out of 51 patients (78%) achieving a CBR response at 12 months. The objective response rate (ORR) was 54.9%, and the stable disease rate was 43.1%, resulting in an overall CBR of 98%. The median overall survival (OS) was 62.9 months (95% CI, 46-NR).
According to Dr. Saby George, professor of oncology and medicine at Roswell Park, the combination therapy also demonstrated a superior safety profile compared with immunotherapy combinations. Common adverse events (AEs) of any grade included diarrhea (70%), hypertension (54%), fatigue (69%), and nausea (51%). The most common grade 3 or 4 AEs were hypertension (33%), ALT elevation (14%), and AST elevation (12%).
Implications for Favorable Risk Patients
Notably, the study enrolled a higher proportion of patients in the IMDC favorable risk category (31 of 45 patients) due to the availability of immunotherapy options for other risk groups. Dr. George suggests that the alternating pazopanib and bevacizumab regimen is a promising treatment option for renal cell carcinoma patients in the favorable risk group.
Mechanism of Action
Pazopanib, a tyrosine kinase inhibitor (TKI), works by blocking vascular endothelial growth factor (VEGF) signaling, a key mechanism for cancer cell growth. Bevacizumab, on the other hand, neutralizes VEGF, potentially extending pazopanib's anti-cancer effects and preventing resistance. The alternating regimen aims to maximize the benefits of both drugs while minimizing the development of resistance.
