PMID- 25456838
OWN - NLM
STAT- MEDLINE
DCOM- 20160128
LR  - 20220311
IS  - 1938-0682 (Electronic)
IS  - 1558-7673 (Linking)
VI  - 13
IP  - 3
DP  - 2015 Jun
TI  - 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.
PG  - 231-8
LID - S1558-7673(14)00212-2 [pii]
LID - 10.1016/j.clgc.2014.09.005 [doi]
AB  - 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((R)) followed by 
      afiniTOR((R)) (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. 
      CONCLUSION: 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.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Thiery-Vuillemin, Antoine
AU  - Thiery-Vuillemin A
AD  - Oncology Department, Jean Minjoz Hospital, Besancon, France. Electronic address: 
      a.thieryvuillemin@mac.com.
FAU - Theodore, Christine
AU  - Theodore C
AD  - Oncology Department, Foch Hospital, Suresnes, France.
FAU - Jacobasch, Lutz
AU  - Jacobasch L
AD  - Private practice, Hematology/Oncology, Dresden, Germany.
FAU - Schmitz, Jorg
AU  - Schmitz J
AD  - Oncology Department, Lindenberg/Ried Clinic, Lindenberg, Germany.
FAU - Papandreou, Christos
AU  - Papandreou C
AD  - Oncology Department, University Hospital of Larissa, Larissa, Greece.
FAU - Guillot, Aline
AU  - Guillot A
AD  - Oncology Institute of Loire, Saint Priest en Jarez, France.
FAU - Emmanouilides, Christos
AU  - Emmanouilides C
AD  - Oncology Department, Interbalkan Hospital, Thessaloniki, Greece.
FAU - Slimane, Khemaies
AU  - Slimane K
AD  - Oncology Department, Novartis Pharma, Paris, France.
FAU - Kelkouli, Nadia
AU  - Kelkouli N
AD  - Oncology Department, Novartis Pharma, Paris, France.
FAU - Kim, Stefano
AU  - Kim S
AD  - Oncology Department, Jean Minjoz Hospital, Besancon, France.
FAU - Nguyen Tan Hon, Thierry
AU  - Nguyen Tan Hon T
AD  - Oncology Department, Jean Minjoz Hospital, Besancon, France.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20141120
PL  - United States
TA  - Clin Genitourin Cancer
JT  - Clinical genitourinary cancer
JID - 101260955
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antineoplastic Agents)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 9008-11-1 (Interferons)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Aged
MH  - Angiogenesis Inhibitors/therapeutic use
MH  - Antineoplastic Agents/*administration & dosage/adverse effects/therapeutic use
MH  - Bevacizumab/therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy/pathology
MH  - Europe
MH  - Everolimus/*administration & dosage/adverse effects/therapeutic use
MH  - Female
MH  - Humans
MH  - Interferons/therapeutic use
MH  - Kidney Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Retrospective Studies
MH  - Survival Analysis
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Bevacizumab
OT  - Everolimus
OT  - Renal cell carcinoma
OT  - Second-line therapy
OT  - Sequential therapy
OT  - mTOR inhibitor
EDAT- 2014/12/03 06:00
MHDA- 2016/01/29 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/06/27 00:00 [received]
PHST- 2014/09/26 00:00 [revised]
PHST- 2014/09/30 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2016/01/29 06:00 [medline]
AID - S1558-7673(14)00212-2 [pii]
AID - 10.1016/j.clgc.2014.09.005 [doi]
PST - ppublish
SO  - Clin Genitourin Cancer. 2015 Jun;13(3):231-8. doi: 10.1016/j.clgc.2014.09.005. 
      Epub 2014 Nov 20.