Evidence map›Paper›PMID 24947924›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2014

The combination of circulating Ang1 and Tie2 levels predicts progression-free survival advantage in bevacizumab-treated patients with ovarian cancer.

Alison Backen, Andrew G Renehan, Andrew R Clamp, Carlo Berzuini, Cong Zhou, Amit Oza, Selina Bannoo, Stefan J Scherer, Rosamonde E Banks, Caroline Dive and 1 more

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04770376 (Prospective Pilot Study for the Evaluation of the Predictive Value of Blood Levels of Angiopoietin 1), which is not on this map. Cited by 40 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 3 pooled it
11.2field-weighted citation impact, top 2% 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.

NCT04770376 unknown statusnot on this mapstarted 2020, after this paper: background citation

Prospective Pilot Study for the Evaluation of the Predictive Value of Blood Levels of Angiopoietin 1 (ANG1) and Endothelial Internal Tunica Cell Kinase 2 (TiE2) in Patients With Ovarian Cancer Treated With Chemotherapy Associated to bevAcizumab

TypeobservationalSponsorIRCCS Azienda Ospedaliero-Universitaria di BolognaRan2020 to 2023Enrolled150ConditionsOvarian CancerArmsObservational study. Blood samples will be collected at scheduled blood draws performed as per clinical practice before each cycle of chemotherapy.
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 79 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 8 institutions in 3 countries.

Alison Backen *Clinical and Experimental Pharmacology, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Withington, Manchester M20 4BX, United Kingdom.
Andrew G Renehan *Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Center, The Christie NHS Foundation Trust, Wilmslow Road, Withington, Manchester, M20 4BX, UK.
Andrew R ClampDept Medical Oncology, University of Manchester and Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK.
Carlo BerzuiniCenter for Biostatistics, Institute of Population Health, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
Cong ZhouClinical and Experimental Pharmacology, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Withington, Manchester M20 4BX, United Kingdom.
Amit OzaBras Family Drug Development Program, Princess Margaret Hospital, 610 University Avenue, Toronto M5G 2M9.
Selina BannooMRC Clinical Trials Unit, Aviation House, 125 Kingsway, London WC2B 6NH.
Stefan J SchererBiocartis SA, EPFL-Quartier de l'Innovation, Bâtimont G, CH-1015 Lausanne.
Rosamonde E BanksLeeds Institute of Cancer and Pathology, St James University Hospital, Leeds LS9 7TF, UK.
Caroline DiveClinical and Experimental Pharmacology, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Withington, Manchester M20 4BX, United Kingdom.
Gordon C JaysonTranslational Angiogenesis Group, University of Manchester and Christie Hospital, Wilmslow Road, Withington, Manchester, M20 4BX, UK.
Cancer Research UK Manchester Institute · GBThe Christie Hospital · GBManchester Academic Health Science Centre · GBMedartis (Switzerland) · CHMRC Clinical Trials Unit at UCL · GBPrincess Margaret Hospital · NZSt James's University Hospital · GBUniversity of Manchester · GB

Funding

Cancer Research UK 19278Cancer Research UK A7966Medical Research Council G0802320Medical Research Council MR/L01629X/1
6 · The paper itself

Abstract

purposeRandomized ovarian cancer trials, including ICON7, have reported improved progression-free survival (PFS) when bevacizumab was added to conventional cytotoxic therapy. The improvement was modest prompting the search for predictive biomarkers for bevacizumab. EXPERIMENTAL

designPretreatment training (n=91) and validation (n=114) blood samples were provided by ICON7 patients. Plasma concentrations of 15 angio-associated factors were determined using validated multiplex ELISAs. Our statistical approach adopted PFS as the primary outcome measure and involved (i) searching for biomarkers with prognostic relevance or which related to between-individual variation in bevacizumab effect; (ii) unbiased determination of cutoffs for putative biomarker values; (iii) investigation of biologically meaningfully predictive combinations of putative biomarkers; and (iv) replicating the analysis on candidate biomarkers in the validation dataset.

resultsThe combined values of circulating Ang1 (angiopoietin 1) and Tie2 (Tunica internal endothelial cell kinase 2) concentrations predicted improved PFS in bevacizumab-treated patients in the training set. Using median concentrations as cutoffs, high Ang1/low Tie2 values were associated with significantly improved PFS for bevacizumab-treated patients in both datasets (median, 23.0 months vs. 16.2; P=0.003) for the interaction of Ang1-Tie2 treatment in Cox regression analysis. The prognostic indices derived from the training set also distinguished high and low probability for progression in the validation set (P=0.008), generating similar values for HR (0.21 vs. 0.27) between treatment and control arms for patients with high Ang1 and low Tie2 values.

conclusionsThe combined values of Ang1 and Tie2 are predictive biomarkers for improved PFS in bevacizumab-treated patients with ovarian cancer. These findings need to be validated in larger trials due to the limitation of sample size in this study.

Indexed as

AdultAgedAngiopoietin-1Antibodies, Monoclonal, HumanizedBevacizumabBiomarkers, TumorDisease-Free SurvivalFemaleHumansMiddle AgedNeoplastic Cells, CirculatingNeovascularization, PathologicOvarian NeoplasmsPrognosisReceptor, TIE-2Vascular Endothelial Growth Factor AAngiopoietin-1ANGPT1 protein, humanAntibodies, Monoclonal, HumanizedBevacizumabBiomarkers, TumorReceptor, TIE-2Vascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID24947924
PMCPMC4154862
OpenAlexW2125853921

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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.