Tian Zhang, MD, Duke Cancer Center, Durham, NC, discusses new studies showing the potential for vascular endothelial growth factor receptor (VEGFR) inhibitors combined with immunotherapy to treat metastatic renal cell carcinoma (RCC). The Phase III CLEAR trial (NCT02811861) investigated the first-line VEGFR inhibitor lenvatinib (len) with the immune checkpoint inhibitor pembrolizumab (pembro) or len and everolimus (eve) versus sunitinib monotherapy. Results demonstrated improved progression-free survival and overall survival, and an objective response rate of approximately 70% in the len + pembro group. Overall, the treatment was well-tolerated with some overlapping toxicities, but could be a suitable option for first-line treatment of advanced RCC. The PDIGREE trial (NCT03793166), currently open for enrolment, is investigating upfront treatment of metastatic RCC with the immune checkpoint inhibitors ipilimumab and nivolumab, followed by the VEGFR inhibitor cabozantinib as second-line treatment. Dr Zhang also discusses the CheckMate 9ER trial (NCT03141177) and the CheckMate 214 trial (NCT02231749). This interview took place during the 2021 Genitourinary Cancers Symposium.