PMID- 26276039
OWN - NLM
STAT- MEDLINE
DCOM- 20160130
LR  - 20151014
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 51
IP  - 16
DP  - 2015 Nov
TI  - Everolimus for patients with metastatic renal cell carcinoma refractory to 
      anti-VEGF therapy: results of a pooled analysis of non-interventional studies.
PG  - 2368-74
LID - S0959-8049(15)00710-8 [pii]
LID - 10.1016/j.ejca.2015.07.030 [doi]
AB  - AIM: To assess the efficacy and safety of everolimus in patients with metastatic 
      renal cell carcinoma (mRCC) who failed one or two anti-VEGF therapies. PATIENTS 
      AND METHODS: Data from four prospective, non-interventional studies conducted in 
      Germany, France, Greece and Austria were pooled for this analysis. Patients with 
      mRCC of any histology (clear cell or non-clear cell) were included. 
      VEGF-refractory patients received everolimus 10mg/day until disease progression 
      or unacceptable toxicity. The primary objective was to determine everolimus 
      efficacy as measured by time to progression (TTP; from baseline to progression). 
      RESULTS: The overall population comprised 632 patients; 493 patients received 
      everolimus in the second-line setting. Most patients were of 
      favourable/intermediate MSKCC risk (91%), had clear cell mRCC (89%), and had 
      undergone nephrectomy (89%). Median TTP was 6.3months (95% confidence interval 
      [CI], 5.9-6.8) for the overall population and 6.4months (95% CI, 5.8-6.9) for the 
      second-line everolimus population. Similarly, median progression-free survival 
      was 5.5months (95% CI, 5.0-6.1) for the overall population and 5.8months (95% CI, 
      5.0-6.4) for second-line everolimus population. Best tumour response (n=349) was 
      complete or partial remission in 12% of patients and stable disease in 59% of 
      patients. Overall population median overall survival (OS) was 11.2months (95% CI, 
      9.0-not reached). Commonly reported adverse events (AEs) (any grade) were 
      stomatitis (25%), anaemia (15%) and asthenia (11%). CONCLUSIONS: Results of this 
      pooled analysis provide evidence of safety and effectiveness of second-line 
      everolimus in routine clinical use and support everolimus as a standard of care 
      for VEGF-refractory patients with mRCC.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Albiges, Laurence
AU  - Albiges L
AD  - Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. 
      Electronic address: laurence.albiges@gustaveroussy.fr.
FAU - Kube, Ulrich
AU  - Kube U
AD  - Private Practice Urology, Chemnitz, Germany.
FAU - Eymard, Jean-Christophe
AU  - Eymard JC
AD  - Institut Jean Godinot, Reims, France.
FAU - Schmidinger, Manuela
AU  - Schmidinger M
AD  - Department of Medicine I, Clinical Division of Oncology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Bamias, Aristotelis
AU  - Bamias A
AD  - Department of Clinical Therapeutics, Athens University, Medical School, Athens, 
      Greece.
FAU - Kelkouli, Nadia
AU  - Kelkouli N
AD  - Novartis Pharma SAS, Paris, France.
FAU - Mraz, Bernhard
AU  - Mraz B
AD  - Novartis Pharma GmbH, Vienna, Austria.
FAU - Florini, Styliani
AU  - Florini S
AD  - Novartis Hellas S.A.C.I., Athens, Greece.
FAU - Guderian, Gernot
AU  - Guderian G
AD  - Novartis Pharma GmbH, Nuremberg, Germany.
FAU - Cattaneo, Agnese
AU  - Cattaneo A
AD  - Novartis Pharma, Origgio, Italy.
FAU - Bergmann, Lothar
AU  - Bergmann L
AD  - University Hospital Frankfurt, Tumor Center Rhein-Main, Frankfurt/Main, Germany.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20150811
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/*therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy/metabolism/secondary
MH  - Chemotherapy, Adjuvant
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - *Drug Resistance, Neoplasm
MH  - Europe
MH  - Everolimus/adverse effects/*therapeutic use
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Kidney Neoplasms/*drug therapy/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Nephrectomy
MH  - Risk Factors
MH  - Time Factors
MH  - Treatment Outcome
MH  - Vascular Endothelial Growth Factor A/*antagonists & inhibitors/metabolism
MH  - Young Adult
OTO - NOTNLM
OT  - Everolimus
OT  - Metastatic renal cell carcinoma
OT  - Non-interventional
OT  - Sequential targeted therapy
EDAT- 2015/08/16 06:00
MHDA- 2016/01/31 06:00
CRDT- 2015/08/16 06:00
PHST- 2015/04/17 00:00 [received]
PHST- 2015/07/17 00:00 [revised]
PHST- 2015/07/21 00:00 [accepted]
PHST- 2015/08/16 06:00 [entrez]
PHST- 2015/08/16 06:00 [pubmed]
PHST- 2016/01/31 06:00 [medline]
AID - S0959-8049(15)00710-8 [pii]
AID - 10.1016/j.ejca.2015.07.030 [doi]
PST - ppublish
SO  - Eur J Cancer. 2015 Nov;51(16):2368-74. doi: 10.1016/j.ejca.2015.07.030. Epub 2015 
      Aug 11.