Evidence map›Paper›PMID 30071865›Full record

Trial reportBreast cancer research : BCR2018

A phase II clinical trial of the Aurora and angiogenic kinase inhibitor ENMD-2076 for previously treated, advanced, or metastatic triple-negative breast cancer.

Jennifer R Diamond, S G Eckhardt, Todd M Pitts, Adrie van Bokhoven, Dara Aisner, Daniel L Gustafson, Anna Capasso, Sharon Sams, Peter Kabos, Kathryn Zolman and 8 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01639248 (A Phase II Study of the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Previously Treated Locally Advanced and Metastatic Triple-Negative Breast Cancer), which is not on this map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

NCT01639248 phase2completednot on this map

A Phase II Study of the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Previously Treated Locally Advanced and Metastatic Triple-Negative Breast Cancer

TypeinterventionalSponsorCASI pharmaceuticals, Inc.Ran2012 to 2017Enrolled41ConditionsTriple Negative Breast CancerArmsENMD-2076
3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  16. The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024
    Review
  17. Review
  18. Article
  19. Seize the engine: Emerging cell cycle targets in breast cancer.Clinical and translational medicine · 2024
    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

18 authors.

Jennifer R DiamondUniversity of Colorado Cancer Center, Aurora, CO, USA. jennifer.diamond@ucdenver.edu.ORCID 0000-0002-0703-2772
S G EckhardtDepartment of Oncology, University of Texas at Austin, Dell Medical School, Austin, TX, USA.
Todd M PittsUniversity of Colorado Cancer Center, Aurora, CO, USA.
Adrie van BokhovenUniversity of Colorado Cancer Center, Aurora, CO, USA.
Dara AisnerUniversity of Colorado Cancer Center, Aurora, CO, USA.
Daniel L GustafsonUniversity of Colorado Cancer Center, Aurora, CO, USA.
Anna CapassoDepartment of Oncology, University of Texas at Austin, Dell Medical School, Austin, TX, USA.
Sharon SamsUniversity of Colorado Cancer Center, Aurora, CO, USA.
Peter KabosUniversity of Colorado Cancer Center, Aurora, CO, USA.
Kathryn ZolmanUniversity of Colorado Cancer Center, Aurora, CO, USA.
Tiffany ColvinUniversity of Colorado Cancer Center, Aurora, CO, USA.
Anthony D EliasUniversity of Colorado Cancer Center, Aurora, CO, USA.
Anna M StornioloIndiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
Bryan P SchneiderIndiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
Dexiang GaoUniversity of Colorado Cancer Center, Aurora, CO, USA.
John J TentlerUniversity of Colorado Cancer Center, Aurora, CO, USA.
Virginia F BorgesUniversity of Colorado Cancer Center, Aurora, CO, USA.
Kathy D MillerIndiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Cancer-associated fibroblasts in estrogen receptor positive breast cancer.R01CA205044 · NCI · UNIVERSITY OF COLORADO DENVER · PI KABOS, PETER · 2016 to 2020
$1.8M
The Development of Novel Individualized Therapy for Triple-Negative Breast CancerK23CA172691 · NCI · UNIVERSITY OF COLORADO DENVER · PI DIAMOND, JENNIFER R. · 2013 to 2017
$859k
The Development of Novel Individualized Therapy for Metastatic Triple Negative BR21CA164617 · NCI · UNIVERSITY OF COLORADO DENVER · PI DIAMOND, JENNIFER R. · 2012 to 2013
$373k
NCI NIH HHS 1K23CA172691-01A1NCI NIH HHS 1R21CA164617-01A1NCI NIH HHS 5P30CA046934-25NCI NIH HHS K23 CA172691NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA205044NCI NIH HHS R21 CA164617
6 · The paper itself

Abstract

backgroundTriple-negative breast cancer (TNBC) remains an aggressive breast cancer subtype with limited treatment options. ENMD-2076 is a small-molecule inhibitor of Aurora and angiogenic kinases with proapoptotic and antiproliferative activity in preclinical models of TNBC.

methodsThis dual-institution, single-arm, two-stage, phase II clinical trial enrolled patients with locally advanced or metastatic TNBC previously treated with one to three prior lines of chemotherapy in the advanced setting. Patients were treated with ENMD-2076 250 mg orally once daily with continuous dosing in 4-week cycles until disease progression or unacceptable toxicity occurred. The primary endpoint was 6-month clinical benefit rate (CBR), and secondary endpoints included progression-free survival, pharmacokinetic profile, safety, and biologic correlates in archival and fresh serial tumor biopsies in a subset of patients.

resultsForty-one patients were enrolled. The 6-month CBR was 16.7% (95% CI, 6-32.8%) and included two partial responses. The 4-month CBR was 27.8% (95% CI, 14-45.2%), and the average duration of benefit was 6.5 cycles. Common adverse events included hypertension, fatigue, diarrhea, and nausea. Treatment with ENMD-2076 resulted in a decrease in cellular proliferation and microvessel density and an increase in p53 and p73 expression, consistent with preclinical observations.

conclusionsSingle-agent ENMD-2076 treatment resulted in partial response or clinical benefit lasting more than 6 months in 16.7% of patients with pretreated, advanced, or metastatic TNBC. These results support the development of predictive biomarkers using archival and fresh tumor tissue, as well as consideration of mechanism-based combination strategies.

trial registrationClinicalTrials.gov, NCT01639248 . Registered on July 12, 2012.

Indexed as

Administration, OralAdultAgedAntineoplastic AgentsAurora Kinase ABiopsyBreastBreast Neoplasms, MaleDiarrheaDisease ProgressionFatigueFemaleHumansHypertensionMaleMiddle AgedAntineoplastic AgentsAURKA protein, humanAurora Kinase AENMD 2076Protein Kinase InhibitorsPyrazolesPyrimidinesAurora kinase inhibitorBreast cancerENMD-2076Triple negative

Identifiers

PMID30071865
PMCPMC6090978

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Registered trials

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.