title: Everolimus and temsirolimus are not the same second-line in metastatic renal cell carcinoma. A systematic review and meta-analysis of literature data.
abstract: BACKGROUND
  Two mTOR inhibitors, TEM and EVE, proved to be active in mRCC but have never been compared in a prospective trial. We aimed to compare their effectiveness in mRCC patients previously treated with a vascular endothelial growth factor receptor tyrosine kinase inhibitor, and performed a systematic review and meta-analysis of available evidence.
  
  
  METHODS
  The MEDLINE/PubMed database was reviewed for studies that compared EVE with TEM from January 2006 to May 2014. Summary hazard ratio (HR) for overall survival (OS) and time to treatment failure (TTF) were calculated using random and fixed effects models depending on the heterogeneity of included studies. Statistical heterogeneity was assessed using the χ(2) test, and inconsistency was quantified with the I(2) statistic. Publication bias was evaluated using the Begg and Egger test.
  
  
  RESULTS
  Four studies were included in the meta-analysis; data of 937 patients were available: 545 received EVE and 392 TEM. Among the included patients, 863 [92%] were treated with sunitinib and 74 [8%] with pazopanib or sorafenib as first-line therapy. In the overall population, treatment with EVE decreased the risk of death by 26% over TEM (HR, 0.74; 95% confidence interval [CI], 0.59-0.93; P = .008). The TTF was evaluable in 692 patients; in this group, treatment with EVE decreased the risk of treatment failure by 30% (HR, 0.70; 95% CI, 0.56-0.88; P = .002). No significant heterogeneity or publication bias was found for OS and TTF.
  
  
  CONCLUSIONS
  In this analysis, we compared EVE with TEM as second-line therapy in mRCC, and report a significant difference between mTOR inhibitors, even if these results need to be confirmed in a prospective trial.
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Department of Medical Oncology, Milan, Italy. Electronic address: roberto.iacovelli@istitutotumori.mi.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Università Politecnica delle Marche, AOU Ospedali Riuniti, Department of Medical Oncology, Ancona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Department of Medical Oncology, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Verzoni
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Department of Medical Oncology, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grassi
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Department of Medical Oncology, Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Testa
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Department of Medical Oncology, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
authors.affiliation: Università Politecnica delle Marche, AOU Ospedali Riuniti, Department of Medical Oncology, Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Department of Medical Oncology, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procopio
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D016206:Databases, Bibliographic; D000068338:Everolimus / Q000627:therapeutic use*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Second-line; Sequence of therapy; mRCC; mTOR inhibitors