PMID- 31887537
OWN - NLM
STAT- MEDLINE
DCOM- 20200803
LR  - 20200929
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Print)
IS  - 0959-8049 (Linking)
VI  - 126
DP  - 2020 Feb
TI  - Outcomes based on age in the phase III METEOR trial of cabozantinib versus 
      everolimus in patients with advanced renal cell carcinoma.
PG  - 1-10
LID - S0959-8049(19)30812-3 [pii]
LID - 10.1016/j.ejca.2019.10.032 [doi]
AB  - BACKGROUND: Cabozantinib improved progression-free survival (PFS), overall 
      survival (OS) and objective response rate (ORR) compared with everolimus in 
      patients with advanced renal cell carcinoma (RCC) after prior antiangiogenic 
      therapy in the phase III METEOR trial (NCT01865747). Limited data are available 
      on the use of targeted therapies in older patients with advanced RCC. METHODS: 
      Efficacy and safety in METEOR were retrospectively analysed for three age 
      subgroups: <65 (n = 394), 65-74 (n = 201) and >/=75 years (n = 63). RESULTS: PFS, 
      OS and ORR were improved with cabozantinib compared with everolimus in all age 
      subgroups. The PFS hazard ratios (HRs) were 0.53 (95% confidence interval [CI]: 
      0.41-0.68), 0.53 (95% CI: 0.37-0.77) and 0.38 (95% CI: 0.18-0.79) for <65, 65-74 
      and >/=75 years, respectively, and the OS HRs were 0.72 (95% CI: 0.54-0.95), 0.66 
      (95% CI: 0.44-0.99) and 0.57 (95% CI: 0.28-1.14). The ORR for cabozantinib versus 
      everolimus was 15% vs 5%, 21% vs 2% and 19% vs 0%, respectively. No significant 
      differences were observed in PFS or OS with age as a categorical or continuous 
      variable. Grade III/IV adverse events (AEs) were generally consistent across 
      subgroups, although fatigue, hypertension and hyponatraemia occurred more 
      frequently in older patients treated with cabozantinib. Dose reductions to manage 
      AEs were more frequent in patients receiving cabozantinib than in those receiving 
      everolimus. Dose reductions and treatment discontinuation due to AEs were more 
      frequent in older patients in both treatment groups. CONCLUSIONS: Cabozantinib 
      improved PFS, OS and ORR compared with everolimus in previously treated patients 
      with advanced RCC, irrespective of age group, supporting use in all age 
      categories. Proactive dose modification and supportive care may help to mitigate 
      AEs in older patients while maintaining efficacy.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Donskov, Frede
AU  - Donskov F
AD  - Aarhus University Hospital, Aarhus, Denmark. Electronic address: 
      Frede.Donskov@auh.rm.dk.
FAU - Motzer, Robert J
AU  - Motzer RJ
AD  - Memorial Sloan Kettering Cancer Center, New York, NY, USA.
FAU - Voog, Eric
AU  - Voog E
AD  - Centre Jean Bernard Clinique Victor Hugo, Le Mans, France.
FAU - Hovey, Elizabeth
AU  - Hovey E
AD  - Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, 
      Australia.
FAU - Grullich, Carsten
AU  - Grullich C
AD  - National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.
FAU - Nott, Louise M
AU  - Nott LM
AD  - Royal Hobart Hospital, Hobart, Australia.
FAU - Cuff, Katharine
AU  - Cuff K
AD  - Princess Alexandra Hospital, Woolloongabba, Australia.
FAU - Gil, Thierry
AU  - Gil T
AD  - Institute Jules Bordet, Brussels, Belgium.
FAU - Jensen, Niels Viggo
AU  - Jensen NV
AD  - Odense Universitetshospital, Odense, Denmark.
FAU - Chevreau, Christine
AU  - Chevreau C
AD  - Institut Universitaire Du Cancer Toulouse, Toulouse, France.
FAU - Negrier, Sylvie
AU  - Negrier S
AD  - Universite Claude Bernard Lyon 1, Centre Leon Berard, Lyon, France.
FAU - Depenbusch, Reinhard
AU  - Depenbusch R
AD  - Onkologische Schwerpunktpraxis Gutersloh, Gutersloh, Germany.
FAU - Bergmann, Lothar
AU  - Bergmann L
AD  - Universitatsklinik Frankfurt Hospital, Frankfurt, Germany.
FAU - Cornelio, Izzy
AU  - Cornelio I
AD  - Exelixis, Alameda, CA, USA.
FAU - Champsaur, Anne
AU  - Champsaur A
AD  - Exelixis, Alameda, CA, USA.
FAU - Escudier, Bernard
AU  - Escudier B
AD  - Gustave Roussy, Villejuif, France.
FAU - Pal, Sumanta
AU  - Pal S
AD  - City of Hope National Medical Center, Duarte, CA, USA.
FAU - Powles, Thomas
AU  - Powles T
AD  - Barts Cancer Institute, Queen Mary University of London, London, UK.
FAU - Choueiri, Toni K
AU  - Choueiri TK
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01865747
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191227
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Anilides)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 1C39JW444G (cabozantinib)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Anilides/adverse effects/*therapeutic use
MH  - Antineoplastic Agents/adverse effects/therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy
MH  - Diarrhea/chemically induced
MH  - Everolimus/adverse effects/*therapeutic use
MH  - Fatigue/chemically induced
MH  - Female
MH  - Humans
MH  - Hypertension/chemically induced
MH  - Kaplan-Meier Estimate
MH  - Kidney Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Outcome Assessment, Health Care/*methods/statistics & numerical data
MH  - Proportional Hazards Models
MH  - Protein Kinase Inhibitors/adverse effects/therapeutic use
MH  - Pyridines/adverse effects/*therapeutic use
MH  - Retrospective Studies
PMC - PMC7521477
MID - NIHMS1624361
OTO - NOTNLM
OT  - Age
OT  - Cabozantinib
OT  - Everolimus
OT  - METEOR
OT  - Renal cell carcinoma
OT  - Tyrosine kinase inhibitor
OT  - Vascular endothelial growth factor receptor
COIS- Conflict of interest statement F.D. certifies that all conflicts of interest, 
      including specific financial interests and relationships and affiliations 
      relevant to the subject matter or materials discussed in the manuscript (e.g. 
      employment/affiliation, grants or funding, consultancies, honoraria, stock 
      ownership or options, expert testimony royalties or patents filed, received or 
      pending), are the following: F.D. received research grant support from Pfizer, 
      Novartis, Ipsen, and Health Research Foundation of Central Denmark Region, 
      outside the submitted work. R.J.M. served in a consultancy or advisory role for 
      Pfizer, Novartis, Merck, Genentech/Roche, Eisai and Exelixis and received 
      research funding from Bristol-Myers Squibb, Pfizer, Genentech/Roche, Eisai, 
      Exelixis and Novartis. K.C. received honoraria from Roche, served in a 
      consultancy or advisory role for Roche and Novartis and received support for 
      travel and accommodation from Roche and Amgen. S.N. received honoraria from 
      Pfizer, Bristol-Myers Squibb, Novartis, Ipsen and Eusa Pharma, outside the 
      submitted work. I.C. and A.C. are employees of Exelixis. B.E. received grant 
      support and personal fees from Bristol-Myers Squibb, Pfizer, Novartis, Ipsen and 
      Eusa. S.P. received honoraria from Astellas Pharma, Medivation and Novartis, 
      served in a consultancy or advisory role for Aveo, Bristol-Myers Squibb, 
      Exelixis, Genentech, Myriad Pharmaceuticals, Novartis and Pfizer and received 
      research funding from Medivation. T.P. served in a consultancy or advisory role 
      for AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Merck and Novartis, and 
      received research funding from AstraZeneca/MedImmune and Roche/Genentech. T.K.C. 
      served in a consultancy or advisory role for Roche, GlaxoSmithKline, Merck, 
      Novartis, Peloton, Pfizer, EMD Serono, Prometheus Laboratories, Corvus, Ipsen, 
      UpToDate, NCCN and Analysis Group, received research funding (institutional and 
      personal) from AstraZeneca, Bayer, BMS, Cerulean, Eisai, Foundation Medicine 
      Inc., Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, 
      GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus Laboratories, 
      Corvus, Calithera, Analysis Group and Takeda, received honoraria from 
      AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation 
      Medicine Inc., Exelixis, Genentech, Roche, GlaxoSmithKline, Merck, Novartis, 
      Peloton, Pfizer, EMD Serono, Prometheus Laboratories, Corvus, Ipsen, UpToDate, 
      NCCN, Analysis Group, NCCN, Michael J. Hennessy (MJH) Associates, Inc (Healthcare 
      Communications Company with several brands such as OncLive and PER), Lpath, 
      Kidney Cancer journal, Clinical Care Options, PlatformQ, Navinata Healthcare, 
      Harborside Press, American Society of Medical Oncology, NEJM, Lancet Oncology and 
      Heron Therapeutics and has received travel, accommodations and expenses in 
      relation to consulting and advisory roles or honoraria; T.K.C.'s institution 
      (Dana-Farber Cancer Institute) may have received additional independent funding 
      or royalties from drug companies potentially involved in research around the 
      subject matter. All other authors declare no conflict of interest.
EDAT- 2019/12/31 06:00
MHDA- 2020/08/04 06:00
PMCR- 2020/09/28
CRDT- 2019/12/31 06:00
PHST- 2019/05/13 00:00 [received]
PHST- 2019/09/19 00:00 [revised]
PHST- 2019/10/30 00:00 [accepted]
PHST- 2019/12/31 06:00 [pubmed]
PHST- 2020/08/04 06:00 [medline]
PHST- 2019/12/31 06:00 [entrez]
PHST- 2020/09/28 00:00 [pmc-release]
AID - S0959-8049(19)30812-3 [pii]
AID - 10.1016/j.ejca.2019.10.032 [doi]
PST - ppublish
SO  - Eur J Cancer. 2020 Feb;126:1-10. doi: 10.1016/j.ejca.2019.10.032. Epub 2019 Dec 
      27.