Evidence map›Paper›PMID 30980733›Full record

Trial reportBritish journal of clinical pharmacology2019

Dynamics of circulating vascular endothelial growth factor-A predict benefit from antiangiogenic cediranib in metastatic or recurrent cervical cancer patients.

Cong Zhou, Sarah Taylor, Jonathan Tugwood, Kathryn Simpson, Gordon C Jayson, Paul Symonds, James Paul, Susan Davidson, Karen Carty, Elaine McCartney and 3 more

Open access · bronzeAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 33% 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

2 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. Trial
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

13 authors at 5 institutions in 1 country.

Cong ZhouDivision of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.ORCID 0000-0002-6938-4685
Sarah TaylorClinical & Experimental Pharmacology Group, Cancer Research UK Manchester Institute and Manchester Centre for Cancer Biomarker Sciences, University of Manchester, UK.
Jonathan TugwoodClinical & Experimental Pharmacology Group, Cancer Research UK Manchester Institute and Manchester Centre for Cancer Biomarker Sciences, University of Manchester, UK.
Kathryn SimpsonClinical & Experimental Pharmacology Group, Cancer Research UK Manchester Institute and Manchester Centre for Cancer Biomarker Sciences, University of Manchester, UK.
Gordon C JaysonDivision of Cancer Sciences, University of Manchester, Christie Hospital NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Paul SymondsDepartment of Cancer Studies, University of Leicester, Leicester, UK.
James PaulCancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Susan DavidsonChristie Hospital NHS Trust, Manchester, UK.
Karen CartyCancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Elaine McCartneyCancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Debbie RaiCancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Caroline DiveClinical & Experimental Pharmacology Group, Cancer Research UK Manchester Institute and Manchester Centre for Cancer Biomarker Sciences, University of Manchester, UK.
Catharine WestDivision of Cancer Sciences, University of Manchester, Christie Hospital NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Cancer Research UK · GBUniversity of Manchester · GBManchester Academic Health Science Centre · GBThe Christie Hospital · GBUniversity of Leicester · GB

Funding

Cancer Research UK 19278Cancer Research UK 25355Cancer Research UK 29569Cancer Research UK A25146Cancer Research UK C1256/A11416Cancer Research UK C5759/A25254Cancer Research UK C5759/A27412
6 · The paper itself

Abstract

aimsThere is a need for predictive and surrogate response biomarkers to support treatment with antiangiogenic vascular endothelial growth factor (VEGF) inhibitors. We aimed to identify a minimally-invasive biomarker predicting benefit from cediranib pretreatment or early during treatment in patients with recurrent or metastatic cervical cancer.

methodsBlood samples were collected before treatment, during treatment and upon disease progression where appropriate from patients enrolled in CIRCCa, a randomised phase II trial of carboplatin and paclitaxel with or without cediranib. Plasma concentrations of VEGF-A, VEGF-receptor 2, Ang1 and Tie2 were measured using multiplex enzyme-linked immunosorbent assay. Pretreatment and temporal changes of the biomarkers were investigated using proportional hazard regression and unsupervised clustering analysis.

resultsSamples (n = 556) from 52 patients were analysed. VEGF-receptor 2 (P = .0006) and Tie2 (P = .04) were downregulated following cediranib, while VEGF-A (P = .0025) was upregulated. High Eastern Cooperative Oncology Group performance status (P = .02, hazard ratio [HR] = 2.15, 95% confidence interval [CI] 1.13-4.09) and low pretreatment Tie2 concentrations (P = .003, HR = 0.57, 95%CI 0.39-0.83) were independent prognostic factors associated with reduced progression-free survival. Two patterns of changes in VEGF-A following cediranib were identified. Patients with elevated VEGF-A in the first 3 treatment cycles, regardless of magnitude, had reduced progression-free survival in the placebo arm but improved survival with the addition of cediranib (P = .019, HR = 0.13, 95% CI 0.02-0.71).

conclusionPatterns of early elevation in plasma VEGF-A should be studied further as a potential biomarker to predict treatment benefit from cediranib.

Indexed as

AdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorDisease ProgressionDrug MonitoringFemaleHumansIndolesMiddle AgedNeoplasm Recurrence, LocalProgression-Free SurvivalQuinazolinesUterine Cervical NeoplasmsVascular Endothelial Growth Factor AYoung AdultBiomarkers, TumorcediranibIndolesQuinazolinesVascular Endothelial Growth Factor AVEGFA protein, humanangiogenesiscediranibcervical cancerCIRCCa trialresponse biomarkervascular endothelial growth factor

Identifiers

PMID30980733
PMCPMC6624436
OpenAlexW2937983743

What OpenQuestion holds

Textmetadata
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.