title: Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: synthesis of findings from two multi-practice chart reviews in the United States.
abstract: BACKGROUND
  Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study compares the effectiveness of these therapies in a multi-practice chart review and synthesizes the findings with those of a similarly designed study.
  
  
  METHODS
  Medical oncologists/hematologists (N = 36) were recruited to review charts for patients aged ≥18 years, received a first-line TKI and initiated second-line targeted therapy in 2010 or later. The primary outcome was time from second-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving second-line everolimus (EVE), temsirolimus (TEM), or TKI as a class, using a Cox proportional hazards model adjusting for type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled, in a meta-analysis, with previously reported HRs for progression-free survival from a chart review with a similar design.
  
  
  RESULTS
  A total of 138, 64 and 79 patients received second-line therapy with EVE, TEM or a TKI, respectively. Adjusting for baseline characteristics, EVE was associated with numerical, but not statistically significant, reductions of 28% (HR = 0.72; 95% CI [0.45-1.16]) and 26% (HR = 0.74; 95% CI [0.48-1.15]) in the hazard of TTF compared to TEM and TKI, respectively. After pooling the HRs from both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (HR = 0.73; 95% CI [0.57-0.93]; and HR = 0.75; 95% CI [0.57-0.98], respectively).
  
  
  CONCLUSIONS
  LIMITATIONS include retrospective analyses with possible missing or erroneous chart data, confounding of unobserved factors due to non-randomization, and limited data for axitinib during the study period.
  
  
  CONCLUSIONS
  In pooled results from two independent multi-practice chart reviews of second-line mRCC treatment, EVE was associated with significantly reduced hazards of treatment failure compared to TEM and to TKIs as a class.
authors.affiliation: Analysis Group Inc. , Boston, MA , USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Signorovitch
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.forename: Peggy L
authors.initials: PL
authors.lastname: Lin
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wong
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Liu
authors.forename: Xufang
authors.initials: X
authors.lastname: Wang
authors.forename: Ken
authors.initials: K
authors.lastname: Culver
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Scott
authors.forename: Eric
authors.initials: E
authors.lastname: Jonasch
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017211:Treatment Failure; D014481:United States
chemical_list: D000970:Antineoplastic Agents; C401859:temsirolimus; D000068338:Everolimus; D020123:Sirolimus
keywords: Comparative effectiveness; Everolimus; Mammalian target of rapamycin inhibitors; Metastatic renal cell carcinoma; Temsirolimus; Tyrosine kinase inhibitors