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Updated: Jan 21, 2026
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
Sequencing and Combination of Systemic Therapy in Metastatic Renal Cell Carcinoma
Guillermo de Velasco1, Axel Bex2, Laurence Albiges3
1Hospital Universitario 12 de Octubre, Madrid, Spain.
Context:
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.
Objective:
A comprehensive (nonsystematic) review to determine the suggested sequence or combinations for the systemic treatment of mRCC.
Evidence Acquisition:
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.
Evidence Synthesis:
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.
Conclusions:
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.
Patient Summary:
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.
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