The tango of immunotherapy and targeted therapy in metastatic renal cell carcinoma

Over the past decade, the mortality rate due to advanced renal cell carcinoma (RCC) has seen a significant decline (1). This has been accomplished mostly due to the rapid transformation of the treatment landscape of advanced clear cell RCC (ccRCC) which comprises 70% to 80% of RCC (2). Therapies targeting vascular endothelial growth factor pathway, mammalian target of rapamycin pathway, and immune checkpoints have replaced interferon-α and high dose interleukin-2 in clinical practice (2). Despite of these advancements, many patients do not benefit from many of these recent drug approvals. The attrition rate of patients from first line to second-line therapy is very high at 50%, and only approximately 25% patients remain alive to allow treatment in the third line therapy setting (3). This has pushed the momentum to bring the most effective therapies to the first-line setting to improve outcomes. One recent strategy to achieve this has been to combine targeted therapies with immunotherapies.