Introduction of additional new agents targeting the vascular endothelial growth factor receptor (VEGFR) and immune checkpoint inhibitors (ICIs) has completely modified the systemic treatment of metastatic renal cell carcinoma (mRCC) during the last years.

A comprehensive (nonsystematic) review to determine the suggested sequence or combinations for the systemic treatment of mRCC.

PubMed and abstracts from main conferences up to December 2018 were reviewed to retrieve the current evidence for treatment of mRCC. Search terms included renal cell carcinoma, systemic therapy, targeted therapy (TT), and immunotherapy.

Marked advances in the treatment of mRCC have been made with novel VEGFR tyrosine kinase inhibitors and multiple ICIs that have been included in the current treatment paradigm of mRCC. Remarkable advance has been made with the combination of double checkpoint blockade. The combination of ipilimumab and nivolumab compared with sunitinib has shown to increase the overall survival in the intermediate- and poor-risk patients based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model.

Double checkpoint blockade with ipilimumab and nivolumab has reported overall survival benefit in IMDC intermediate- and poor-risk patients, providing a durable response for a subset of patients. VEGF inhibitors remain the standard of care for favorable-risk patients in the first line. In the immediate future, more consolidated data on combination of VEGF-TT plus ICIs may show similar robust benefit with different safety profiles.

Multiple drugs and sequences are now accepted as effective treatment for metastatic renal cell carcinoma (mRCC). Combination of immune checkpoint inhibitors has shown to increase the overall survival in treatment-naïve mRCC patients. Combinations of immunotherapy and antiangiogenics may be another option in the near future. Outcomes of the first line will determine the sequence, although the best sequence has yet to be defined.

European urology oncology. 2019 Jul 31 [Epub ahead of print]

Guillermo de Velasco, Axel Bex, Laurence Albiges, Thomas Powles, Brian I Rini, Robert J Motzer, Daniel Y C Heng, Bernard Escudier

Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address: ., Royal Free London NHS Fountation Turst, London, UK; UCL DIvision of Surgery and Interventional Science, London, UK., Institut Gustave Roussy, Villejuif, France., Barts Cancer Institute, London, UK., Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA., Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Tom Baker Cancer Center, Calgary, Canada.