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Oncologist. 2019 Mar;24(3):338-348. doi: 10.1634/theoncologist.2018-0267. Epub 2018 Aug 29.

The Current and Evolving Landscape of First-Line Treatments for Advanced Renal Cell Carcinoma.

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Centro Integral Oncológico Clara Campal and START Madrid, Madrid, Spain
Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy.
Clinic for Hematology, Hemostaseology, Oncology & Stem Cell Transplantation, Medical School of Hannover, Hannover, Germany.
Department of Medical Oncology, Gustave Roussy, Villejuif, France.


Agents targeting the vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), as well as the mammalian target of rapamycin (mTOR) and immune checkpoint receptor programmed death 1 (PD-1) signaling pathway have improved clinical outcomes for patients with advanced renal cell carcinoma (RCC). The VEGFR tyrosine kinase inhibitors (TKIs) pazopanib and sunitinib are FDA-approved first-line treatment options for advanced RCC; however, other treatment options in this setting are available, including the recently approved combination of nivolumab (anti-PD-1) and ipilimumab (anti-cytotoxic T-lymphocyte-associated protein-4 [CTLA-4]) for patients with intermediate or poor risk. Unfortunately, treatment guideline recommendations provide little guidance to aid first-line treatment choice. In addition, several ongoing randomized phase III trials of investigational first-line regimens may complicate the RCC treatment paradigm if these agents gain approval. This article reviews clinical trial and real-world evidence for currently approved and investigational first-line treatment regimens for advanced RCC and provides clinical evidence to aid first-line treatment selection. IMPLICATIONS FOR PRACTICE: Vascular endothelial growth factor receptor tyrosine kinase inhibitors are approved by the U.S. Food and Drug Administration as first-line treatment options for advanced renal cell carcinoma; however, the treatment paradigm is rapidly evolving. The combination of nivolumab plus ipilimumab was recently approved for intermediate- and poor-risk patients, and other combination strategies and novel first-line agents will likely be introduced soon.


Immune checkpoint inhibitors; Immunotherapy; Renal cell carcinoma; Targeted therapy; Tyrosine kinase inhibitors

[Available on 2020-03-01]

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

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