Both immune checkpoint inhibitors (ICIs) and VEGF receptor inhibitors are approved for advanced renal cell carcinoma (RCC) treatment and can cause cardiovascular events (CVs). This randomized study of avelumab plus axitinib vs. sunitinib used prospective monitoring of LVEF and serum cardiac biomarkers to assess for the development of major adverse CV events. The results indicate patients with high baseline troponin T levels and who receive combination ICI and VEGF receptor inhibitor therapy should be monitored closely for adverse cardiac events.