Dr. McDermott on VEGF/PD-1 Inhibition in RCC

David F. McDermott, MD, director of the Biologic Therapy and Cutaneous Oncology Programs at Beth Israel Deaconess Medical Center, professor of medicine, Harvard Medical School, discusses the research behind combining VEGF inhibitors with PD-1/PD-L1 inhibitors in renal cell carcinoma treatment.

In 2015, the standard of care for most patients with advanced kidney cancer was a VEGF inhibitor for treatment-naïve patients, followed by a PD-1 inhibitor with nivolumab for patients who fail a VEGF inhibitor, explains McDermott. Over the last several years, a wave of new data from phase I to phase III trials show that there are better outcomes when VEGF inhibitors are combined with PD-1 inhibitors rather than VEGF inhibitors alone.

One such study is the KEYNOTE-426 trial, which compared pembrolizumab and axitinib (Inlyta) with sunitinib (Sutent). The combination showed benefits in objective response rate, progression-free survival, and overall survival. This combination is now a standard approach, as well as axitinib plus avelumab (Bavencio), says McDermott.

Another positive study looked at the PD-L1 inhibitor atezolizumab (Tecentriq) combined with bevacizumab (Avastin). When combining VEGF inhibitors with PD-1/PD-L1 inhibitors, improvements in survival likely occur because bringing PD-1 inhibition up to the frontline setting makes treatment more active in aggressive tumors, according to McDermott. Giving PD-1 inhibition improves survival outcomes and allows more patients to reach second-line therapy, concludes McDermott.