Roswell Park–Designed Treatment Regimen Doubles Progression-Free Survival in Metastatic Kidney Cancer

A phase 1/2 clinical trial for patients with metastatic kidney cancer demonstrated that a novel two-agent treatment regimen developed at Roswell Park Comprehensive Cancer Center more than doubled progression-free survival compared with single-agent treatment. Saby George, MD, FACP, Professor of Oncology and Medicine and Director of Network Clinical Trials at Roswell Park, served as Principal Investigator of the study and delivered the findings of the phase 2 portion in a poster presentation at the European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain. 

Patients in the single-arm study had received no prior therapy. During each 10-week treatment cycle, they received pazopanib (brand name Votrient), which is FDA-approved for the treatment of metastatic clear cell renal carcinoma (mccRCC), on days 1 to 28. Pazopanib works by shutting down vascular endothelial growth factor (VEGF) signaling, which supports the growth of new blood vessels that feed the tumor. An increase in VEGF activity is thought to produce resistance to pazopanib, so the patients also received bevacizumab (brand name Avastin) on days 36 to 50 during the cycle, to neutralize VEGF in the hope of extending progression-free survival (PFS).

In clinical trials that supported FDA approval of pazopanib for advanced RCC, the median PFS was 11.1 months. The median PFS for patients who received the combination therapy was 23.3 months.

Study participants were assigned to groups of various risk levels using the International Metastatic Renal Cell Carcinoma Database (IMDC). “Because immunotherapy options were available to patients in other risk groups, the phase 2 group included more patients in the Favorable Risk category,” explains Dr George. “The encouraging results suggest that alternating pazopanib with bevacizumab is a promising treatment regimen for renal cell carcinoma patients in the Favorable Risk group.”

Data from the clinical trial showed equal or superior efficacy compared with immunotherapy combinations or sunitinib (brand name Sutent) administered as a single agent, and superior safety compared with immunotherapy combinations, in patients in the IMDC Favorable Risk group.

Earlier results from a phase 1 study to evaluate the safety of this combination were presented at the 2019 Genitourinary Cancer Symposium of the American Society of Clinical Oncology (ASCO).

Based on preclinical studies at Roswell Park, the clinical trial enrolled 51 patients and was conducted at 5 US cancer centers, including Roswell Park, the University of Pittsburgh, the University of Kansas, the Medical College of Wisconsin, and Karmanos Cancer Center in Detroit. Prior preclinical research was funded by Roswell Park/the Roswell Park Alliance Foundation, the National Cancer Institute, and Novartis.