Dr. McDermott on TKI/Immunotherapy Combinations 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 combination of VEGF TKIs and PD-1 inhibitors in advanced renal cell carcinoma (RCC).

Preclinically, VEGF inhibitors were found to suppress regulatory T cells, increase dendritic cell activity, and improve T cell tumor infiltration, thereby increasing immune response, explains McDermott. This served as the rationale to explore combinations of VEGF inhibitors and PD-1 inhibitors.

The addition of PD-1 inhibitors to VEGF inhibitors showed a higher complete response (CR) rate than either agent alone. For example, in the phase III KEYNOTE-426 trial of pembrolizumab (Keytruda) plus axitinib (Inlyta) compared with sunitinib (Sutent), investigators reported a CR rate of 5.8% and 1.9%, respectively.

Moreover, the addition of PD-1 inhibitors into the frontline setting increases the number of patients who could potentially benefit from the approach compared with a sequenced approach after VEGF monotherapy, concludes McDermott.