Evidence map›Paper›PMID 25989278›Full record

SynthesisBritish journal of cancer2015

Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer.

A Rowland, M M Dias, M D Wiese, G Kichenadasse, R A McKinnon, C S Karapetis, M J Sorich

Open access · hybridAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
167citing papers in PubMed, 9 pooled it
15.2field-weighted citation impact, top 1% 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

167 citing papers in PubMed, 9 syntheses or guidelines pooled it, 323 citations in OpenAlex.

  1. Pooled it
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  7. Guideline
  8. Molecular Biomarkers for the Evaluation of Colorectal Cancer.American journal of clinical pathology · 2017
    Guideline
  9. Pooled it
  10. Trial
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  12. Encorafenib Plus Cetuximab as a New Standard of Care for Previously TreatedJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Trial
  13. Expanded Low Allele FrequencyClinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Trial
  14. Response to Anti-EGFR Therapy in Patients with BRAF non-V600-Mutant Metastatic Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
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  17. Efficacy and Tolerability of First-Line Cetuximab Plus Leucovorin, Fluorouracil, and Oxaliplatin (FOLFOX-4) Versus FOLFOX-4 in Patients WithJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018
    Trial
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107 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

A Rowland1] Department of Clinical Pharmacology, School of Medicine, Flinders University, Bedford Park, Adelaide, South Australia 5042, Australia [2] Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.
M M Dias1] Department of Clinical Pharmacology, School of Medicine, Flinders University, Bedford Park, Adelaide, South Australia 5042, Australia [2] School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
M D WieseSchool of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
G KichenadasseFlinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.
R A McKinnonFlinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.
C S KarapetisFlinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.
M J Sorich1] Department of Clinical Pharmacology, School of Medicine, Flinders University, Bedford Park, Adelaide, South Australia 5042, Australia [2] Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.
Flinders University · AUUniversity of South Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetastatic colorectal cancer (mCRC) that harbours a BRAF V600E mutation (BRAF MT) is associated with poorer outcomes. However, whether this mutation is predictive of treatment benefit from anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is uncertain.

methodsWe conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) published up to July 2014 that evaluated the effect of BRAF MT on the treatment benefit from anti-EGFR mAbs for mCRC.

resultsSeven RCTs met the inclusion criteria for assessment of overall survival (OS), whereas eight RCTs met the inclusion criteria for assessment of progression-free survival (PFS). For RAS WT/BRAF MT tumours, the hazard ratio for OS benefit with anti-EGFR mAbs was 0.97 (95% CI; 0.67-1.41), whereas the hazard ratio was 0.81 (95% CI; 0.70-0.95) for RAS WT/BRAF WT tumours. However, the test of interaction (P=0.43) was not statistically significant, highlighting that the observed differences in the effect of anti-EGFR mAbs on OS according to the BRAF mutation status may be due to chance alone. Regarding PFS benefit with anti-EGFR mAbs, the hazard ratio was 0.86 (95% CI; 0.61-1.21) for RAS WT/BRAF MT tumours as compared with 0.62 (95% CI; 0.50-0.77) for RAS WT/BRAF WT tumours (test of interaction, P=0.07).

interpretationThis meta-analysis demonstrates that there is insufficient evidence to definitively state that RAS WT/BRAF MT individuals attain a different treatment benefit from anti-EGFR mAbs for mCRC compared with RAS WT/BRAF WT individuals. As such, there are insufficient data to justify the exclusion of anti-EGFR mAb therapy for patients with RAS WT/BRAF MT mCRC.

Indexed as

MutationAntibodies, MonoclonalColorectal NeoplasmsErbB ReceptorsHumansNeoplasm MetastasisProto-Oncogene Proteins B-rafRandomized Controlled Trials as TopicAntibodies, MonoclonalBRAF protein, humanEGFR protein, humanErbB ReceptorsProto-Oncogene Proteins B-raf

Identifiers

PMID25989278
PMCPMC4580381
OpenAlexW4250745281

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.