A phase 1/2 clinical trial revealed that a novel two-agent treatment regimen developed at Roswell Park Comprehensive Cancer Center significantly extended progression-free survival (PFS) in patients with metastatic kidney cancer. The study, presented at the European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain, showed that the combination of pazopanib and bevacizumab more than doubled the PFS compared to single-agent pazopanib.
The single-arm study involved patients who had not received prior therapy. The treatment cycle consisted of 10 weeks, during which patients received pazopanib on days 1-28 to inhibit vascular endothelial growth factor (VEGF) signaling. To counter potential resistance due to increased VEGF activity, bevacizumab was administered on days 36-50 to neutralize VEGF, aiming to prolong PFS.
Significant Improvement in Progression-Free Survival
Results from the clinical trial indicated a median PFS of 23.3 months for patients treated with the pazopanib and bevacizumab combination. This is a notable improvement compared to the 11.1 months of median PFS observed in previous clinical trials that led to FDA approval of pazopanib as a monotherapy for advanced renal cell carcinoma (RCC).
Saby George, MD, FACP, Professor of Oncology and Medicine and Director of Network Clinical Trials at Roswell Park, who served as the Principal Investigator of the study, noted that the phase 2 group included more patients in the Favorable Risk category according to the International Metastatic Renal Cell Carcinoma Database (IMDC). He stated, "The encouraging results suggest that alternating pazopanib with bevacizumab is a promising treatment regimen for renal cell carcinoma patients in the Favorable Risk group."
Efficacy and Safety Profile
The data from the clinical trial indicated that the combination therapy had equal or superior efficacy compared to immunotherapy combinations or sunitinib administered as a single agent. Furthermore, the combination demonstrated a superior safety profile compared with immunotherapy combinations, specifically in patients within the IMDC Favorable Risk group.
Trial Design and Patient Population
The clinical trial enrolled 51 patients across five U.S. cancer centers, including Roswell Park, the University of Pittsburgh, the University of Kansas, the Medical College of Wisconsin, and Karmanos Cancer Center in Detroit. The trial was based on preclinical studies conducted at Roswell Park. Earlier phase 1 study results, which evaluated the safety of this combination, were presented at the 2019 Genitourinary Cancer Symposium of the American Society of Clinical Oncology (ASCO).
