Investigators at the Dana-Farber Cancer Institute recently completed a phase 3 clinical trial that could lead to changes in the standard treatment protocol for advanced kidney cancer. The trial tested a combination of the immunotherapy medication, avelumab, and axitinib, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), against sunitinib, another VEGFR TKI, which is currently the standard treatment for advanced clear-cell renal carcinoma, the most common form of kidney cancer.

This trial was the first to combine avelumab with an agent that targets one of the receptors controlling angiogenesis. VEGFR inhibitors, like axitinib and sunitinib, are designed to block the blood supply to tumors, starving them of essential nutrients. Immunotherapy medications, like avelumab, block an immune checkpoint called PD-L1, and activate the body’s T-cells so they are more effective in fighting cancer cells.

The randomized study consisted of 886 patients with previously untreated, advanced renal cell carcinoma. Results of the study showed that patients receiving the combination of avelumab and axitinib had a higher response rate than those receiving sunitinib, causing greater tumor shrinkage. The results for patients whose cancer cells were positive for the PD-L1 checkpoint showed a median progression-free survival (PFS) of 13.8 months in the combination group compared to 7.2 months in the sunitinib group. The PFS for the overall population was the same for the combination group, and was 8.4 months in the sunitinib group. Tumor shrinkage was 55.2% in the combination group compared to 25.5% in the sunitinib group who were positive for PD-L1.  

While PFS improved with the drug combination, researchers plan to continue follow ups with patients to determine if the combination of medications extends the overall survival rate compared to the standard regimen. Senior author of the study, Toni Choueiri, MD, hopes the results will lead to an FDA approval for the combination in the near future and a shift in the standard of care for patients with this difficult-to-treat cancer.