title: Everolimus Versus Temsirolimus in Metastatic Renal Cell Carcinoma After Progression With Previous Systemic Therapies.
abstract: BACKGROUND
  Everolimus is an approved agent for use after disease progression with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) in patients with metastatic renal cell carcinoma. With recently published trials showing efficacy of nivolumab and cabozantinib in the second-line therapy setting, the use of everolimus will likely move to the third- or fourth-line therapy setting. Temsirolimus has occasionally been used instead of everolimus for many reasons, including financial considerations, assurance of patient compliance given its intravenous administration, its toxicity profile, patient performance status, and patient or physician preference. However, efficacy of everolimus and temsirolimus in this setting have not been compared in a randomized trial. The results from retrospective studies have been inconsistent.
  
  
  METHODS
  We identified patients treated with a first-line VEGFR-TKI for metastatic renal cell carcinoma and then treated with either everolimus or temsirolimus on progression from the databases of 2 large academic cancer centers. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of second-line treatment using the Kaplan-Meier method.
  
  
  RESULTS
  A total of 90 patients received either everolimus (n = 59; 66%) or temsirolimus (n = 31; 34%) after progression during first-line VEGFR-TKI therapy. The patient and disease characteristics were similar in both groups. The median PFS was not different, but OS was superior with everolimus compared with temsirolimus (24.2 months vs. 12.1 months; hazard ratio, 0.58; P = .047).
  
  
  CONCLUSIONS
  Our results bolster existing guidelines supporting everolimus over temsirolimus as salvage therapy after previous systemic therapies.
authors.affiliation: Department of Internal Medicine, University of Utah Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Shiven B
authors.initials: SB
authors.lastname: Patel
authors.affiliation: Pharmacotherapy Outcomes Research Center, College of Pharmacy, The University of Utah, Salt Lake City, UT.
authors.forename: David D
authors.initials: DD
authors.lastname: Stenehjem
authors.affiliation: Department of Internal Medicine, University of Utah Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: David M
authors.initials: DM
authors.lastname: Gill
authors.affiliation: Department of Internal Medicine, University of Utah Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Srinivas K
authors.initials: SK
authors.lastname: Tantravahi
authors.affiliation: Department of Pathology and ARUP Laboratories, The University of Utah, Salt Lake City, UT.
authors.forename: Archana M
authors.initials: AM
authors.lastname: Agarwal
authors.affiliation: Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA.
authors.forename: JoAnne
authors.initials: J
authors.lastname: Hsu
authors.affiliation: Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA.
authors.forename: Winston
authors.initials: W
authors.lastname: Vuong
authors.affiliation: Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA.
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.affiliation: Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT. Electronic address: neeraj.agarwal@hci.utah.edu.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012189:Retrospective Studies; D016879:Salvage Therapy; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D000068338:Everolimus; D020123:Sirolimus
keywords: Genitourinary cancer; Kidney cancer; Outcomes; Salvage therapy; mTORi