Evidence map›Paper›PMID 31444999›Full record

Trial reportCancer medicine2019

Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma.

Eudocia Q Lee, Alona Muzikansky, Dan G Duda, Sarah Gaffey, Jorg Dietrich, Lakshmi Nayak, Ugonma N Chukwueke, Rameen Beroukhim, Lisa Doherty, Caroline Kane Laub and 9 more

Open access · goldAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 2 pooled it
2.3field-weighted citation impact, top 12% 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

34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.

  1. Pooled it
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  17. Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.International journal of molecular sciences · 2024
    Review
  18. Review
  19. Review
  20. Targeting of endothelial cells in brain tumours.Clinical and translational medicine · 2023
    Review
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

19 authors at 2 institutions in 1 country.

Eudocia Q LeeDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.ORCID 0000-0003-3355-5179
Alona MuzikanskyHarvard Medical School, Boston, Massachusetts.
Dan G DudaHarvard Medical School, Boston, Massachusetts.
Sarah GaffeyDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Jorg DietrichHarvard Medical School, Boston, Massachusetts.
Lakshmi NayakDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Ugonma N ChukwuekeDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Rameen BeroukhimDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Lisa DohertyDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Caroline Kane LaubDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Debra LaFrankieDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Brittney FontanaDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Jennifer StefanikDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Sandra RulandDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Victoria CarusoDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Jennifer BrunoDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Keith LigonDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
David A ReardonDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Patrick Y WenDana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Harvard University · USDana-Farber Brigham Cancer Center · US

Funding

Takeda Oncology
6 · The paper itself

Abstract

backgroundResponses to bevacizumab in glioblastoma (GBM) are not durable. Plasma levels of basic fibroblast growth factor (bFGF) increase at the time of tumor progression. By targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, Src, and FGF receptor pathways, ponatinib may potentially help to overcome some of the putative mechanisms of adaptive resistance.

methodsWe performed a phase II trial of ponatinib in patients with bevacizumab-refractory GBM and variants. Adult patients with Karnofsky performance score (KPS) ≥60, measurable disease, and normal organ and marrow function received 45 mg ponatinib daily. No limit on the number of prior therapies but only one prior bevacizumab-containing regimen was allowed. Primary endpoint was 3-month progression-free survival. Plasma biomarkers of angiogenesis and inflammation were evaluated before and after treatment.

resultsThe study closed after the first stage. Fifteen patients enrolled: median age 61 [27-74]; median KPS 80 [70-90]; median number of prior relapses 2 [2-4]. Three-month progression-free survival rate was 0, median overall survival was 98 days [95% CI 56, 257], and median PFS was 28 days [95% CI 27, 30]. No responses were seen. The most common grade ≥3 adverse events included fatigue (n = 3), hypertension (2), and lipase elevation (2). Ponatinib treatment significantly increased plasma VEGF, soluble (s)VEGFR1, sVEGFR2, sTIE2, interferon gamma (IFNγ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-8, and IL-10 and decreased sVEGFR2.

conclusionsPonatinib was associated with minimal activity in bevacizumab-refractory GBM patients. Circulating biomarker data confirmed pharmacodynamic changes and suggested that resistance to ponatinib may be related to an increase in inflammatory cytokines.

Indexed as

AdultAgedAngiogenesis InhibitorsBevacizumabBiomarkersBrain NeoplasmsCytokinesDrug Resistance, NeoplasmFemaleGlioblastomaHumansImidazolesKarnofsky Performance StatusMaleMiddle AgedProgression-Free SurvivalAngiogenesis InhibitorsBevacizumabBiomarkersCytokinesImidazolesKDR protein, humanponatinibProtein Kinase InhibitorsPyridazinesReceptor, TIE-2TEK protein, humanVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2VEGFA protein, humanangiogenesisbevacizumab-refractoryFGFRglioblastomaVEGFR

Identifiers

PMID31444999
PMCPMC6792497
OpenAlexW2969980725

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.