Evidence map›Paper›PMID 37329221›Full record

Trial reportCancer medicine2023

Clinical and metabolomic characterization of Brivanib-Induced hypertension in metastatic colorectal cancer.

Jodi I Rattner, Karen A Kopciuk, Hans J Vogel, Patricia A Tang, Jeremy D Shapiro, Dongsheng Tu, Derek J Jonker, Lillian L Siu, Chris J O'Callaghan, Oliver F Bathe

Open access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.4field-weighted citation impact, top 16% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. 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

10 authors at 5 institutions in 4 countries.

Jodi I RattnerCumming School of Medicine, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.ORCID 0000-0002-5291-7254
Karen A KopciukDepartment of Mathematics and Statistics, Faculty of Science, University of Calgary, Calgary, Alberta, Canada.
Hans J VogelDepartment Biological Sciences, Faculty of Science, University of Calgary, Calgary, Alberta, Canada.
Patricia A TangCumming School of Medicine, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.
Jeremy D ShapiroDepartment of Medical Oncology, Carbini Hospital, Melbourne, Victoria, Australia.
Dongsheng TuDepartment of Community Health & Epidemiology, Queens University, Kingston, Ontario, Canada.
Derek J JonkerDivision of Medical Oncology, Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada.
Lillian L SiuDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Chris J O'CallaghanDepartment of Community Health & Epidemiology, Queens University, Kingston, Ontario, Canada.
Oliver F BatheCumming School of Medicine, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.
University of Calgary · CAQueen's University · CAOttawa Hospital · CAPrincess Margaret Cancer Centre · CAWestern Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTrials of tyrosine kinase inhibitors (TKI) have not demonstrated dramatic benefits in advanced colorectal cancer (CRC), and this may be a function of poor patient selection. TKI-induced hypertension is reportedly a surrogate marker for treatment benefit for some tumor types. Our objective was to determine whether hypertension was associated with benefit in the context of CRC treatment, and also to gain insight on the pathogenesis of TKI-induced hypertension by monitoring associated changes in the circulating metabolome. PATIENTS AND

methodsClinical data were acquired from clinical trial patients with metastatic CRC randomized to cetuximab ± the TKI brivanib (N = 750). Outcomes were evaluated as a function of treatment-induced hypertension. For metabolomic studies, plasma samples were taken at baseline, as well as at 1, 4, and 12 weeks after treatment initiation. Samples were submitted to gas chromatography-mass spectrometry to identify treatment-related metabolomic changes associated with TKI-induced hypertension, compared to pre-treatment baseline. A model based on changes in metabolite concentrations was generated using orthogonal partial least squares discriminant analysis (OPLS-DA).

resultsIn the brivanib treated group, 95 patients had treatment-related hypertension within 12 weeks of initiating treatment. TKI-induced hypertension was not associated with a significantly higher response rate, nor was it associated with improved progression-free or overall survival. In metabolomic studies, 386 metabolites were identified. There were 29 metabolites that changed with treatment and distinguished patients with and without TKI-induced hypertension. The OPLS-DA model for brivanib-induced hypertension was significant and robust (R

conclusionTKI-induced hypertension was not associated with clinical benefit in metastatic CRC. We have identified changes in the metabolome that are associated with the development of worsening brivanib-induced hypertension that may be useful in future efforts of characterizing this toxicity.

Indexed as

Colonic NeoplasmsColorectal NeoplasmsRectal NeoplasmsAlanineHumansMetabolomeMetabolomicsTriazinesAlaninebrivanibTriazinescancer biomarkerchemotherapycolorectal cancerhypertensionmetabolomicssurvival

Identifiers

PMID37329221
PMCPMC10469666
OpenAlexW4381046697

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.