title: Efficacy and Safety of Sequential Use of Everolimus in Patients With Metastatic Renal Cell Carcinoma Previously Treated With Bevacizumab With or Without Interferon Therapy: Results From the European AVATOR Study.
abstract: BACKGROUND
  Everolimus is a mammalian target of rapamycin (mTOR) inhibitor. It gained approval based on the results of the RECORD-1 (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism 1) trial, which included patients with metastatic renal cell carcinoma (mRCC) whose disease progressed after receiving vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Bevacizumab is a monoclonal antibody targeting angiogenesis that is approved in patients with mRCC. The sequence of everolimus second-line therapy after failure of bevacizumab ± interferon (IFN) first-line therapy has not yet been studied.
  
  
  METHODS
  AVAstin(®) followed by afiniTOR(®) (AVATOR) was a noninterventional retrospective multicenter European observational study of 42 unselected patients with mRCC who were previously or currently treated with everolimus after failure of bevacizumab ± IFN. The primary end point was everolimus progression-free survival (PFS). Secondary end points were related to the overall survival (OS) of patients receiving the drug sequence and everolimus treatment and safety.
  
  
  RESULTS
  Exploring the duration of second-line everolimus treatment, 63.8% of patients received at least 3 months of everolimus and 28.8% received at least 8 months of treatment. At the time of data analysis, 15 patients (36%) were still receiving everolimus, 40% had stopped because of progressive disease, and 24% had discontinued treatment for other reasons. Patients receiving everolimus after bevacizumab experienced a median PFS of 17 months (95% confidence interval [CI], 5 [not reached]). Median OS was not reached with everolimus second-line therapy. At 32 months after the start of first-line therapy, 53.3% of patients were still alive. All grades of common adverse events (AEs) were consistent with the known safety profile of everolimus.
  
  
  CONCLUSIONS
  The AVATOR-studied sequence displayed a longer than expected median PFS. Further prospective exploratory studies need to be performed to confirm these encouraging results in a larger cohort of patients.
authors.affiliation: Oncology Department, Jean Minjoz Hospital, Besançon, France. Electronic address: a.thieryvuillemin@mac.com.
authors.forename: Antoine
authors.initials: A
authors.lastname: Thiery-Vuillemin
authors.affiliation: Oncology Department, Foch Hospital, Suresnes, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Theodore
authors.affiliation: Private practice, Hematology/Oncology, Dresden, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Jacobasch
authors.affiliation: Oncology Department, Lindenberg/Ried Clinic, Lindenberg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmitz
authors.affiliation: Oncology Department, University Hospital of Larissa, Larissa, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Papandreou
authors.affiliation: Oncology Institute of Loire, Saint Priest en Jarez, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Guillot
authors.affiliation: Oncology Department, Interbalkan Hospital, Thessaloniki, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Emmanouilides
authors.affiliation: Oncology Department, Novartis Pharma, Paris, France.
authors.forename: Khemaies
authors.initials: K
authors.lastname: Slimane
authors.affiliation: Oncology Department, Novartis Pharma, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Kelkouli
authors.affiliation: Oncology Department, Jean Minjoz Hospital, Besançon, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Kim
authors.affiliation: Oncology Department, Jean Minjoz Hospital, Besançon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Nguyen Tan Hon
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005060:Europe; D000068338:Everolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D007372:Interferons; D000068338:Everolimus
keywords: Bevacizumab; Everolimus; Renal cell carcinoma; Second-line therapy; Sequential therapy; mTOR inhibitor