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

Nityam Rathi, Benjamin L. Maughan, Neeraj Agarwal, Umang Swami

Abstract

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.