Evidence map›Paper›PMID 24335920›Full record

ArticleBritish journal of cancer2014

Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer.

D J Jonker, C S Karapetis, C Harbison, C J O'Callaghan, D Tu, R J Simes, D P Malone, C Langer, N Tebbutt, T J Price and 7 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 2 pooled it
4.9field-weighted citation impact, top 4% 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

41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.

  1. Pooled it
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  10. Towards Multiomics-Based Dissection of Anti-EGFR Sensitivity in Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
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  15. The Role of EREG/EGFR Pathway in Tumor Progression.International journal of molecular sciences · 2021
    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

17 authors at 2 institutions in 2 countries.

D J JonkerThe Ottawa Hospital Research Institute, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
C S KarapetisFlinders Medical Centre and Flinders University, Flinders Drive, Bedford Park, Adelaide, SA 5042, Australia.
C HarbisonResearch and Development, Bristol-Myers Squibb, 100 Nassau Park Boulevard, Princeton, NJ 08540, USA.
C J O'CallaghanNCIC - Clinical Trials Group, Queens University, Cancer Research Institute, 10 Stuart Street, Kingston, ON K7P 3E3, Canada.
D TuNCIC - Clinical Trials Group, Queens University, Cancer Research Institute, 10 Stuart Street, Kingston, ON K7P 3E3, Canada.
R J SimesNational Health and Medical Research Council Clinical Trials Centre, University of Sydney, ABN 15 211 513 464, Camperdown, NSW 1450, Australia.
D P MaloneResearch and Development, Bristol-Myers Squibb, 100 Nassau Park Boulevard, Princeton, NJ 08540, USA.
C LangerGenetech Inc., 1 Dna Way, South San Francisco, CA 94080, USA.
N TebbuttAustin Health and University of Melbourne, 145 Studley Road, Heidelberg, VIC 3084, Australia.
T J PriceThe Queen Elizabeth Hospital and University of Adelaide, 28 Woodville Road, Woodville South SA 5011, Australia.
J ShapiroCabrini Hospital and Monash University, Isabella Street, Malvern, VIC 3144, Australia.
L L SiuPrincess Margaret Hospital and University of Toronto, 610 University Avenue, Suite 5-718, Toronto, ON M5G 2M9, Canada.
R P W WongCancercare Manitoba, St Boniface General Hospital, 409 Tache Avenue, Rm L1-102, Winnipeg, MB R2H 2A6, Canada.
G BjarnasonSunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
M J MoorePrincess Margaret Hospital and University of Toronto, 610 University Avenue, Suite 5-718, Toronto, ON M5G 2M9, Canada.
J R ZalcbergPeter MacCallum Cancer Centre, Australasian Gastrointestinal Trials Group, University of Melbourne, 1 Street Andrews Place, East Melbourne, VIC 3002, Australia.
S Khambata-FordResearch and Development, Bristol-Myers Squibb, 100 Nassau Park Boulevard, Princeton, NJ 08540, USA.
Health Sciences Centre · CAPeter MacCallum Cancer Centre · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAnti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit.

methodsTumour samples from a phase III clinical trial of cetuximab plus best supportive care (BSC) vs BSC alone (CO.17) were analysed for EREG mRNA gene expression. Predictive effects of high vs low EREG on OS and progression-free survival (PFS) were examined for treatment-biomarker interaction.

resultsBoth EREG and K-ras status were ascertained in 385 (193 cetuximab, 192 BSC) tumour samples. Within the high EREG and K-ras wild-type status ('co-biomarker')-positive group (n=139, 36%), median PFS was 5.4 vs 1.9 months (hazard ratio (HR) 0.31; P<0.0001), and median OS was 9.8 vs 5.1 months (HR 0.43; P<0.001) for cetuximab vs BSC, respectively. In the rest (n=246, 64%), PFS (HR 0.82; P=0.12) and OS (HR 0.90; P=0.45) were not significantly different. Test for treatment interaction showed a larger cetuximab effect on OS (HR 0.52; P=0.007) and PFS (HR 0.49; P=0.001) in the co-biomarker-positive group.

conclusionIn pre-treated K-ras wild-type status colorectal cancer, patients with high EREG gene expression appear to benefit more from cetuximab therapy compared with low expression. Epiregulin as a selective biomarker requires further evaluation.

Indexed as

AdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedBiomarkers, TumorCetuximabClinical Trials, Phase III as TopicColorectal NeoplasmsDisease-Free SurvivalEpidermal Growth FactorEpiregulinFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedAntibodies, Monoclonal, HumanizedBiomarkers, TumorCetuximabEpidermal Growth FactorEpiregulinEREG protein, humanras Proteins

Identifiers

PMID24335920
PMCPMC3915121
OpenAlexW2055443426

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.