Evidence map›Paper›PMID 25673697›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015

A Translational, Pharmacodynamic, and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer.

Taofeek K Owonikoko, Suresh S Ramalingam, Daniel L Miller, Seth D Force, Gabriel L Sica, Jennifer Mendel, Zhengjia Chen, Andre Rogatko, Mourad Tighiouart, R Donald Harvey and 14 more

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 15% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. YAP1 Expression in SCLC Defines a Distinct Subtype With T-cell-Inflamed Phenotype.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2021
    Article
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  8. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 1 institution in 1 country.

Taofeek K OwonikokoDepartment of Hematology and Medical Oncology, Emory University, Atlanta, Georgia. Winship Cancer Institute of Emory University, Atlanta, Georgia.
Suresh S RamalingamDepartment of Hematology and Medical Oncology, Emory University, Atlanta, Georgia. Winship Cancer Institute of Emory University, Atlanta, Georgia.
Daniel L MillerWinship Cancer Institute of Emory University, Atlanta, Georgia. Department of Surgery, Emory University, Atlanta, Georgia.
Seth D ForceWinship Cancer Institute of Emory University, Atlanta, Georgia. Department of Surgery, Emory University, Atlanta, Georgia.
Gabriel L SicaWinship Cancer Institute of Emory University, Atlanta, Georgia. Department of Pathology, Emory University, Atlanta, Georgia.
Jennifer MendelWinship Cancer Institute of Emory University, Atlanta, Georgia.
Zhengjia ChenWinship Cancer Institute of Emory University, Atlanta, Georgia. Department of Statistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Andre RogatkoCedars Sinai Medical Center, Los Angeles, California.
Mourad TighiouartCedars Sinai Medical Center, Los Angeles, California.
R Donald HarveyDepartment of Hematology and Medical Oncology, Emory University, Atlanta, Georgia. Winship Cancer Institute of Emory University, Atlanta, Georgia.
Sungjin KimWinship Cancer Institute of Emory University, Atlanta, Georgia.
Nabil F SabaDepartment of Hematology and Medical Oncology, Emory University, Atlanta, Georgia. Winship Cancer Institute of Emory University, Atlanta, Georgia.
Allan PickensDepartment of Surgery, Emory University, Atlanta, Georgia.
Madhusmita BeheraDepartment of Hematology and Medical Oncology, Emory University, Atlanta, Georgia.
Robert W FuDepartment of Hematology and Medical Oncology, Emory University, Atlanta, Georgia.
Michael R RossiDepartment of Pathology, Emory University, Atlanta, Georgia. Department of Radiation Oncology, Emory University, Atlanta, Georgia.
William F AuffermannDepartment of Radiology, Emory University, Atlanta, Georgia.
William E TorresDepartment of Radiology, Emory University, Atlanta, Georgia.
Rabih BecharaDivision of Interventional Pulmonology, Emory University, Atlanta, Georgia.
Xingming DengWinship Cancer Institute of Emory University, Atlanta, Georgia. Department of Radiation Oncology, Emory University, Atlanta, Georgia.
Shi-Yong SunDepartment of Hematology and Medical Oncology, Emory University, Atlanta, Georgia. Winship Cancer Institute of Emory University, Atlanta, Georgia.
Haian FuWinship Cancer Institute of Emory University, Atlanta, Georgia. Department of Pharmacology, Emory University, Atlanta, Georgia.
Anthony A GalWinship Cancer Institute of Emory University, Atlanta, Georgia. Department of Pathology, Emory University, Atlanta, Georgia.
Fadlo R KhuriDepartment of Hematology and Medical Oncology, Emory University, Atlanta, Georgia. Winship Cancer Institute of Emory University, Atlanta, Georgia. fkhuri@emory.edu.
Cedars-Sinai Medical Center · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Suresh S Ramalingam · 2009 to 2026
$47.5M
Targeting Microtubules and HDAC6 in NSCLCP01CA116676 · NCI · EMORY UNIVERSITY · PI KHURI, FADLO RAJA · 2006 to 2012
$8.0M
Therapeutic potential of mTOR kinase inhibitors in lung cancerR01CA160522 · NCI · EMORY UNIVERSITY · PI SUN, SHI-YONG · 2012 to 2016
$1.9M
NCATS NIH HHS UL1 TR000124NCI NIH HHS 3P01 CA116676-05S1NCI NIH HHS P01 CA116676NCI NIH HHS P30 CA138292NCI NIH HHS R01 CA160522
6 · The paper itself

Abstract

purposeThe altered PI3K/mTOR pathway is implicated in lung cancer, but mTOR inhibitors have failed to demonstrate efficacy in advanced lung cancer. We studied the pharmacodynamic effects of everolimus in resectable non-small cell lung cancer (NSCLC) to inform further development of these agents in lung cancer. EXPERIMENTAL

designWe enrolled 33 patients and obtained baseline tumor biopsy and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging followed by everolimus treatment (5 or 10 mg daily, up to 28 days), or without intervening treatment for controls. Target modulation by everolimus was quantified in vivo and ex vivo by comparing metabolic activity on paired PET scans and expression of active phosphorylated forms of mTOR, Akt, S6, eIF4e, p70S6K, 4EBP1, and total Bim protein between pretreatment and posttreatment tissue samples.

resultsThere were 23 patients on the treatment arm and 10 controls; median age 64 years; 22 tumors (67%) were adenocarcinomas. There was a dose-dependent reduction in metabolic activity (SUVmax: 29.0%, -21%, -24%; P = 0.014), tumor size (10.1%, 5.8%, -11.6%; P = 0.047), and modulation of S6 (-36.1, -13.7, -77.0; P = 0.071) and pS6 (-41.25, -61.57, -47.21; P = 0.063) in patients treated in the control, 5-mg, and 10-mg cohorts, respectively. Targeted DNA sequencing in all patients along with exome and whole transcriptome RNA-seq in an index patient with hypersensitive tumor was employed to further elucidate the mechanism of everolimus activity.

conclusionsThis "window-of-opportunity" study demonstrated measurable, dose-dependent, biologic, metabolic, and antitumor activity of everolimus in early-stage NSCLC.

Indexed as

AdultAgedAntineoplastic AgentsBiomarkersCarcinoma, Non-Small-Cell LungDNA Mutational AnalysisEverolimusFemaleFluorodeoxyglucose F18HumansLung NeoplasmsMaleMiddle AgedMutationNeoplasm StagingPositron-Emission TomographyAntineoplastic AgentsBiomarkersEverolimusFluorodeoxyglucose F18

Identifiers

PMID25673697
PMCPMC4401630
OpenAlexW2085143940

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.