Evidence map›Paper›PMID 25742472›Full record

Trial reportBritish journal of cancer2015

Correlation of extended RAS and PIK3CA gene mutation status with outcomes from the phase III AGITG MAX STUDY involving capecitabine alone or in combination with bevacizumab plus or minus mitomycin C in advanced colorectal cancer.

T J Price, M A Bruhn, C K Lee, J E Hardingham, A R Townsend, K P Mann, J Simes, A Weickhardt, J W Wrin, K Wilson and 5 more

Open access · hybridAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report 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 17 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 2 pooled it
2.7field-weighted citation impact, top 8% 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

17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. International journal of molecular sciences · 2019
    Article
  11. Article
  12. Article
  13. Article
  14. World journal of gastroenterology · 2018
    Article
  15. Article
  16. K-RAS and N-RAS mutations in testicular germ cell tumors.Bosnian journal of basic medical sciences · 2017
    Article
  17. 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

15 authors at 6 institutions in 3 countries.

T J Price1] Haematology-Oncology Department, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia [2] School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia.
M A BruhnSchool of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
C K LeeNHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW 2050, Australia.
J E Hardingham1] Haematology-Oncology Department, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia [2] School of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
A R Townsend1] Haematology-Oncology Department, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia [2] School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia.
K P MannNHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW 2050, Australia.
J SimesNHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW 2050, Australia.
A Weickhardt1] Austin Health, Heidelberg, VIC 3084, Australia [2] Ludwig Institute for Cancer Research, Heidelberg, VIC 3084, Australia.
J W WrinHaematology-Oncology Department, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia.
K WilsonNHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW 2050, Australia.
V GebskiNHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW 2050, Australia.
G Van HazelSir Charles Gardiner Hospital, Perth, WA, Australia.
B RobinsonChristchurch Hospital, Christchurch, New Zealand.
D CunninghamRoyal Marsden Hospital, London, UK.
N C Tebbutt1] Austin Health, Heidelberg, VIC 3084, Australia [2] Ludwig Institute for Cancer Research, Heidelberg, VIC 3084, Australia.
The University of Sydney · AUNational Health and Medical Research Council · AUChristchurch Hospital · NZRoyal Marsden Hospital · GBSir Charles Gairdner Hospital · AUThe University of Adelaide · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMutations affecting RAS genes are now established predictive markers of nonresponse to anti-EGFR antibodies in advanced CRC. This analysis assessed the prognostic and predictive impact of extended RAS and PIK3CA gene mutation status in patients receiving capecitabine plus or minus bevacizumab (±mitomycin C) in the randomised phase III MAX study.

methodsDNA was extracted from archival macrodissected formalin-fixed paraffin-embedded tumour tissue. Mutation status was determined using pyrosequencing, confirmed with Sanger sequencing (for equivocal RAS) and correlated with efficacy outcomes. Predictive analyses were undertaken using a test for interaction involving both C vs CB+CBM.

resultsOf the available 280 of the 471 (59.4%) patients, mutations in KRAS exons 2, 3 and 4 and NRAS 2, 3 and 4 were as follows: 32%, 2.9%, 2.2%, 1.4%, 0.7% and 0% (total RAS MT 39%). The PIK3CA MT rate was 7.5% exon 9 and 3.6% exon 20. Extended RAS gene mutation status (WT vs MT) had no prognostic impact for PFS (HR 0.91 (0.71-1.17)) or OS (HR 0.95 (0.71-1.25)). The RAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS (HR 0.56 (0.37-0.85) for RAS MT and HR 0.69 (0.5-0.97) for RAS WT; P for interaction 0.50). The PIK3CA mutation was neither predictive for bevacizumab effect nor prognostic.

conclusionOf KRAS exon 2 WT patients, 10% had additional RAS mutations. Neither all RAS gene mutation status nor PIK3CA mutation status was prognostic for PFS or OS, or predictive of bevacizumab outcome in patients with advanced CRC.

Indexed as

Genes, rasMutationAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCapecitabineClass I Phosphatidylinositol 3-KinasesColorectal NeoplasmsDeoxycytidineDNA, NeoplasmFemaleFluorouracilHumansAntibodies, Monoclonal, HumanizedBevacizumabCapecitabineClass I Phosphatidylinositol 3-KinasesDeoxycytidineDNA, NeoplasmFluorouracilMitomycinPhosphatidylinositol 3-KinasesPIK3CA protein, human

Identifiers

PMID25742472
PMCPMC4366893
OpenAlexW2014590712

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.