title: Sequencing of agents for metastatic renal cell carcinoma: can we customize therapy?
abstract: BACKGROUND
  The expanding armamentarium of agents for the therapy of advanced clear cell renal cell carcinoma (RCC) warrants further investigation of optimal patient selection.
  
  
  OBJECTIVE
  To analyze the second and subsequent line of targeted therapies for advanced RCC while integrating clinical and molecular markers and imaging.
  
  
  METHODS
  Data were acquired from research published in peer-reviewed literature or presented at major conferences.
  
  
  RESULTS
  Following first-line vascular endothelial growth factor (VEGF) inhibitors, second-line therapy with everolimus, a mammalian target of rapamycin inhibitor, and axitinib, a VEGF receptor tyrosine kinase inhibitor, have demonstrated benefits in progression-free survival (PFS). Sorafenib, pazopanib, and axitinib have demonstrated extension of PFS following cytokines. Optimal patient selection based on biomarkers is undergoing investigation. Clinical trials evaluating novel agents and combinations should be preferred.
  
  
  CONCLUSIONS
  Currently, the sequence of therapy is based on patient and physician decision, which may be influenced by comorbidities and toxicity profiles.
authors: Texas Oncology and Veterans Affairs Medical Center, Baylor College of Medicine, 501 Medical Center Blvd., Webster, TX 77598, USA. guru.sonpavde@usoncology.com
authors: Guru
authors: G
authors: Sonpavde
authors: Toni K
authors: TK
authors: Choueiri
authors: Bernard
authors: B
authors: Escudier
authors: Vincenzo
authors: V
authors: Ficarra
authors: Thomas E
authors: TE
authors: Hutson
authors: Peter F
authors: PF
authors: Mulders
authors: Jean-Jacques
authors: JJ
authors: Patard
authors: Brian I
authors: BI
authors: Rini
authors: Michael
authors: M
authors: Staehler
authors: Cora N
authors: CN
authors: Sternberg
authors: Christian G
authors: CG
authors: Stief
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000379:methods*; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D042442:Vascular Endothelial Growth Factors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases