title: Advances in treatment of metastatic renal cell carcinoma.
abstract: Multiple agents, including vascular endothelial growth factor (VEGF) inhibitors and mammalian target of rapamycin inhibitors have been approved over the past decade for the treatment of metastatic renal cell carcinoma (mRCC). Here, we focus on nivolumab, cabozantinib, and lenvatinib plus everolimus, agents that have recently emerged with positive clinical data leading to 'Food and Drug Administration approval or pending approval in mRCC. We also review the development of novel agents of interest showing promise in mRCC as part of combination therapy'.
  
  
  
  Nivolumab and cabozantinib both offer improved survival over everolimus in the second-line treatment of mRCC. Lenvatinib plus everolimus has similarly shown encouraging survival benefits in a phase II trial for the second-line setting. Novel combinations in mRCC, including dual immune checkpoint blockade, VEGF and programmed death 1 inhibition, VEGF and vaccine therapy, dual angiogenic blockade, and VEGF-directed therapy with nanoparticle-containing camptothecin have shown promising activity in early-phase trials.
  
  
  
  Multiple promising agents are available in the treatment of mRCC. The appropriate sequencing of agents in the treatment of mRCC may become further elucidated by future studies that prospectively analyze potential biomarkers to identify patients who will derive the greatest benefit from VEGF, mammalian target of rapamycin, or checkpoint inhibitors.
authors.affiliation: aDepartment of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, USAbDepartment of Internal Medicine, Istanbul Medeniyet University Goztepe Research and Training Hospital, Istanbul, Turkey.
authors.forename: Jun
authors.initials: J
authors.lastname: Gong
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gerendash
authors.forename: Nazli
authors.initials: N
authors.lastname: Dizman
authors.forename: Abrar
authors.initials: A
authors.lastname: Khan
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
mesh_terms: D000813:Anilides / Q000008:administration & dosage; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D019468:Disease Management; D000068338:Everolimus / Q000008:administration & dosage; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D000077594:Nivolumab; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D011804:Quinolines / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000813:Anilides; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011725:Pyridines; D011804:Quinolines; C558660:cabozantinib; D000077594:Nivolumab; D000068338:Everolimus; C531958:lenvatinib