Evidence map›Paper›PMID 25526733›Full record

Trial reportNeuro-oncology2015

A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K.

Daniel J Ma, Evanthia Galanis, S Keith Anderson, David Schiff, Timothy J Kaufmann, Patrick J Peller, Caterina Giannini, Paul D Brown, Joon H Uhm, Steven McGraw and 5 more

Open access · bronzeAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed, 5 pooled it
6.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

100 citing papers in PubMed, 5 syntheses or guidelines pooled it, 164 citations in OpenAlex.

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40 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 7 institutions in 1 country.

Daniel J MaMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Evanthia GalanisMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
S Keith AndersonMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
David SchiffMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Timothy J KaufmannMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Patrick J PellerMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Caterina GianniniMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Paul D BrownMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Joon H UhmMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Steven McGrawMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Kurt A JaeckleMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Patrick J FlynnMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Keith L LigonMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Jan C BucknerMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Jann N SarkariaMayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.).
Jacksonville College · USMayo Clinic in Florida · USUniversity of Virginia · USAlliance Data (United States) · USDana-Farber Cancer Institute · USThe University of Texas MD Anderson Cancer Center · USWinnMed · US

Funding

Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis · 2014 to 2026
$177.3M
CANCER AND LEUKEMIA GROUP B MINORITY SATELLITE SUPPLEMENU10CA031946 · NCI · UNIVERSITY OF CHICAGO · PI BERTAGNOLLI, MONICA M · 1985 to 2013
$158.4M
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3M
Statistics CoreU10CA180882 · NCI · MAYO CLINIC ROCHESTER · PI Sumithra Jay Mandrekar · 2014 to 2026
$115.0M
TRANSLATIONAL RESEARCHU10CA025224 · NCI · MAYO CLINIC ROCHESTER · PI BUCKNER, JAN C · 1985 to 2013
$85.0M
CANCER &LEUKEMIA GROUP B STATISTICAL CENTERU10CA033601 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SARGENT, DANIEL J. · 1985 to 2013
$69.4M
Mayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2M
SUPPLEMENTU10CA037404 · NCI · MAYO CLINIC ROCHESTER · PI LOPRINZI, CHARLES L · 1985 to 2014
$34.8M
Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WENDY Beth LONDON · 2013 to 2026
$33.5M
W METRO-MINNEAPOLIS COMMUNITY CLINICAL ONCOLOGY PROGRAMU10CA035267 · NCI · PARK NICOLLET INSTITUTE · PI LEACH, JOSEPH · 1985 to 2014
$23.2M
Targeted MV-CEA as a Potent Antitumor Agent against GBMP50CA108961 · NCI · MAYO CLINIC ROCHESTER · PI O'NEILL, BRIAN PATRICK · 2004 to 2015
$22.5M
Paul Calabresi Program in Clinical/Translational Research at Mayo ClinicK12CA090628 · NCI · MAYO CLINIC ROCHESTER · PI WEROHA, SARAVUT · 2001 to 2025
$19.7M
NCATS NIH HHS UL1 TR000135NCI NIH HHS CA-108961NCI NIH HHS CA-165962NCI NIH HHS CA-25224NCI NIH HHS CA31946NCI NIH HHS CA33601NCI NIH HHS CA-35103NCI NIH HHS CA-35267NCI NIH HHS CA-37404NCI NIH HHS K12 CA090628NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA165962NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180882
6 · The paper itself

Abstract

backgroundThe mammalian target of rapamycin (mTOR) functions within the phosphatidylinositol-3 kinase (PI3K)/Akt pathway as a critical modulator of cell survival. This clinical trial evaluated the combination of the mTOR inhibitor everolimus with conventional temozolomide (TMZ)-based chemoradiotherapy.

methodsNewly diagnosed patients with glioblastoma multiforme were eligible for this single arm, phase II study. Everolimus (70 mg/wk) was started 1 week prior to radiation and TMZ, followed by adjuvant TMZ, and continued until disease progression. The primary endpoint was overall survival at 12 months, and secondary endpoints were toxicity and time to progression. Eleven patients were imaged with 3'-deoxy-3'-(18)F-fluorothymidine ((18)FLT)-PET/CT before and after the initial 2 doses of everolimus before initiating radiation/TMZ. Imaged patients with sufficient tumor samples also underwent immunohistochemical and focused exon sequencing analysis.

resultsThis study accrued 100 evaluable patients. Fourteen percent of patients had grade 4 hematologic toxicities. Twelve percent had at least one grade 4 nonhematologic toxicity, and there was one treatment-related death. Overall survival at 12 months was 64% and median time to progression was 6.4 months. Of the patients who had (18)FLT-PET data, 4/9 had a partial response after 2 doses of everolimus. Focused exon sequencing demonstrated that (18)FLT-PET responders were less likely to have alterations within the PI3K/Akt/mTOR or tuberous sclerosis complex/neurofibromatosis type 1 pathway compared with nonresponders.

conclusionCombining everolimus with conventional chemoradiation had moderate toxicity. (18)FLT-PET studies suggested an initial antiproliferative effect in a genetically distinct subset of tumors, but this did not translate into an appreciable survival benefit compared with historical controls treated with conventional therapy.

Indexed as

Antineoplastic AgentsBrain NeoplasmsDacarbazineDrug Therapy, CombinationEverolimusGlioblastomaHumansPositron-Emission TomographyPrognosisSurvival AnalysisTemozolomideTOR Serine-Threonine KinasesTreatment OutcomeAntineoplastic AgentsDacarbazineEverolimusMTOR protein, humanTemozolomideTOR Serine-Threonine KinaseseverolimusFLT-PETglioblastomamTOR

Identifiers

PMID25526733
PMCPMC4588750
OpenAlexW2102614717

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.