PMID- 29016998
OWN - NLM
STAT- MEDLINE
DCOM- 20190130
LR  - 20220331
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 20
IP  - 2
DP  - 2018 Jan 22
TI  - Phase II study of cabozantinib in patients with progressive glioblastoma: subset 
      analysis of patients naive to antiangiogenic therapy.
PG  - 249-258
LID - 10.1093/neuonc/nox154 [doi]
AB  - BACKGROUND: Cabozantinib is a tyrosine kinase inhibitor with activity against 
      vascular endothelial growth factor receptor 2 (VEGFR2) and MET that has 
      demonstrated clinical activity in advanced solid tumors. This open-label, phase 
      II trial evaluated cabozantinib in patients with recurrent or refractory 
      glioblastoma (GBM). METHODS: Patients were initially enrolled at a starting dose 
      of 140 mg/day, but the starting dose was amended to 100 mg/day because of 
      toxicity. Treatment continued until disease progression or unacceptable toxicity. 
      The primary endpoint was objective response rate assessed by an independent 
      radiology facility using modified Response Assessment in Neuro-Oncology criteria. 
      Additional endpoints included duration of response, 6-month and median 
      progression-free survival, overall survival, and safety. RESULTS: Among 152 
      patients naive to prior antiangiogenic therapy, the objective response rate was 
      17.6% and 14.5% in the 140 mg/day and 100 mg/day groups, respectively, which did 
      not meet the predefined statistical target for success. The proportions of 
      patients alive and progression free at 6 months were 22.3% and 27.8%, 
      respectively. Median progression-free survival was 3.7 months in both groups, and 
      median overall survival was 7.7 months and 10.4 months, respectively. The 
      incidence of grade 3/4 adverse events (AEs) was 79.4% and 84.7% in the 140 mg/day 
      and 100 mg/day groups, respectively, and dose reductions due to AEs were 
      experienced by 61.8% and 72.0%, respectively. Common grade 3/4 AEs included 
      fatigue, diarrhea, and palmar-plantar erythrodysesthesia syndrome. CONCLUSIONS: 
      Cabozantinib showed evidence of clinical activity in patients with recurrent GBM 
      naive to antiangiogenic therapy, although the predefined statistical target for 
      success was not met. At the starting doses assessed, AEs were frequently managed 
      with dose reductions. CLINICAL TRIALS REGISTRATION NUMBER: NCT00704288 
      (https://www.clinicaltrials.gov/ct2/show/NCT00704288).
CI  - (c) The Author(s) 2017. Published by Oxford University Press on behalf of the 
      Society for Neuro-Oncology.
FAU - Wen, Patrick Y
AU  - Wen PY
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Drappatz, Jan
AU  - Drappatz J
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - de Groot, John
AU  - de Groot J
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Prados, Michael D
AU  - Prados MD
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Reardon, David A
AU  - Reardon DA
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Schiff, David
AU  - Schiff D
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Chamberlain, Marc
AU  - Chamberlain M
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Mikkelsen, Tom
AU  - Mikkelsen T
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Desjardins, Annick
AU  - Desjardins A
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Holland, Jaymes
AU  - Holland J
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Ping, Jerry
AU  - Ping J
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Weitzman, Ron
AU  - Weitzman R
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
FAU - Cloughesy, Timothy F
AU  - Cloughesy TF
AD  - Center for Neuro-Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, 
      Massachusetts (P.Y.W, J.D.); The University of Texas MD Anderson Cancer Center, 
      Houston, Texas (J.dG.); University of California, San Francisco, Helen Diller 
      Cancer Center Building, San Francisco, California (M.D.P.); Duke University, 
      Durham, North Carolina (D.A.R., A.D.); Neuro-Oncology Center, University of 
      Virginia Health System, Charlottesville, Virginia (D.S.); University of 
      Washington, Department of Neurology, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington (M.C.); Henry Ford Health System, Detroit, Michigan (T.M.); 
      Exelixis, South San Francisco, California (J.H., J.P., R.W.); The Ronald Reagan 
      UCLA Medical Center, Los Angeles, California (T.F.C.).
LA  - eng
SI  - ClinicalTrials.gov/NCT00704288
GR  - P50 CA211015/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Anilides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 1C39JW444G (cabozantinib)
SB  - IM
CIN - doi: 10.1093/neuonc/nox151
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/*therapeutic use
MH  - Anilides/*therapeutic use
MH  - Data Analysis
MH  - Disease-Free Survival
MH  - Female
MH  - Glioblastoma/*drug therapy
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Pyridines/*therapeutic use
MH  - Treatment Outcome
PMC - PMC5777496
OTO - NOTNLM
OT  - antiangiogenic
OT  - cabozantinib
OT  - naive
OT  - progressive glioblastoma
OT  - recurrent
EDAT- 2017/10/11 06:00
MHDA- 2019/01/31 06:00
PMCR- 2017/08/14
CRDT- 2017/10/11 06:00
PHST- 2017/10/11 06:00 [pubmed]
PHST- 2019/01/31 06:00 [medline]
PHST- 2017/10/11 06:00 [entrez]
PHST- 2017/08/14 00:00 [pmc-release]
AID - 4082715 [pii]
AID - nox154 [pii]
AID - 10.1093/neuonc/nox154 [doi]
PST - ppublish
SO  - Neuro Oncol. 2018 Jan 22;20(2):249-258. doi: 10.1093/neuonc/nox154.