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

Emiliano Calvo, Camillio Porta, Viktor Grünwald, Bernard Escudier

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Publication statusAccepted/In press - Jan 1 2018


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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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