title: Real-World Effectiveness of Everolimus Subsequent to Different First Targeted Therapies for the Treatment of Metastatic Renal Cell Carcinoma: Synthesis of Retrospective Chart Reviews.
abstract: BACKGROUND
  The effect of first targeted therapy on outcomes with second targeted therapy for metastatic renal cell carcinoma is not well known. The purpose of this study was to compare outcomes for patients receiving a second targeted therapy with everolimus by type of first targeted therapy.
  
  
  METHODS
  Data were drawn from 3 separate retrospective chart reviews conducted in 2011, 2012, and 2014. Inclusion criteria and study design were similar across the 3 studies. To be included in this analysis, patients had to meet the following criteria: aged ≥ 18 years; received first targeted therapy with pazopanib, sunitinib, or sorafenib; and received second targeted therapy with everolimus. Overall survival, time to treatment failure, and time to treatment discontinuation outcomes were measured from second targeted therapy initiation. Outcomes were compared among treatment groups by Cox proportional hazard models adjusting for demographic and clinical characteristics. Hazard ratios for overall survival, time to treatment failure, and time to treatment discontinuation obtained from the 3 chart reviews were synthesized in meta-analyses.
  
  
  RESULTS
  Of 696 patients treated with everolimus as second targeted therapy, 605 patients received first targeted therapy with sunitinib/sorafenib and 91 with pazopanib. After synthesizing the hazard ratios from all studies in meta-analyses, there were no significant differences in study outcomes between patients receiving sunitinib/sorafenib versus those receiving pazopanib as first targeted therapy.
  
  
  CONCLUSIONS
  There were no significant differences among outcomes while receiving second targeted therapy with everolimus for patients treated with pazopanib versus sunitinib/sorafenib as first targeted therapy.
authors.affiliation: City of Hope Comprehensive Cancer Center, Duarte, CA.
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.affiliation: Analysis Group Inc, Boston, MA. Electronic address: James.Signorovitch@analysisgroup.com.
authors.forename: James E
authors.initials: JE
authors.lastname: Signorovitch
authors.affiliation: Analysis Group Inc, Boston, MA.
authors.forename: William M
authors.initials: WM
authors.lastname: Reichmann
authors.affiliation: Analysis Group Inc, Boston, MA.
authors.forename: Nanxin
authors.initials: N
authors.lastname: Li
authors.affiliation: Analysis Group Inc, Boston, MA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Koo
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ.
authors.forename: Jose Ricardo
authors.initials: JR
authors.lastname: Perez
authors.affiliation: US Oncology Research, Comprehensive Cancer Centers of Nevada, Las Vegas, NV.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012189:Retrospective Studies; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; C516667:pazopanib; D000068338:Everolimus; D000077157:Sorafenib; D000077210:Sunitinib
keywords: Discontinuation; Kidney cancer; Overall survival; Progression-free survival; Tyrosine kinase inhibitor; mTOR inhibitor