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https://hdl.handle.net/2440/90759
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dc.contributor.author | Price, T. | - |
dc.contributor.author | Bruhn, M. | - |
dc.contributor.author | Lee, C. | - |
dc.contributor.author | Hardingham, J. | - |
dc.contributor.author | Townsend, A. | - |
dc.contributor.author | Mann, K. | - |
dc.contributor.author | Simes, J. | - |
dc.contributor.author | Weickhardt, A. | - |
dc.contributor.author | Wrin, J. | - |
dc.contributor.author | Wilson, K. | - |
dc.contributor.author | Gebski, V. | - |
dc.contributor.author | Van Hazel, G. | - |
dc.contributor.author | Robinson, B. | - |
dc.contributor.author | Cunningham, D. | - |
dc.contributor.author | Tebbutt, N. | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | British Journal of Cancer, 2015; 112(6):963-970 | - |
dc.identifier.issn | 0007-0920 | - |
dc.identifier.issn | 1532-1827 | - |
dc.identifier.uri | http://hdl.handle.net/2440/90759 | - |
dc.description | Presented in part at the American Society of Clinical Oncology annual meeting, Chicago 31 May to 3 June 2014. | - |
dc.description.abstract | BACKGROUND: Mutations 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. METHODS: DNA 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. RESULTS: Of 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. CONCLUSION: Of 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. | - |
dc.description.statementofresponsibility | 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, V Gebski, G Van Hazel, B Robinson, D Cunningham and N C Tebbutt | - |
dc.language.iso | en | - |
dc.publisher | Nature Publishing Group | - |
dc.rights | © 2015 Cancer Research UK | - |
dc.source.uri | http://dx.doi.org/10.1038/bjc.2015.37 | - |
dc.subject | Humans | - |
dc.subject | Colorectal Neoplasms | - |
dc.subject | Mitomycin | - |
dc.subject | Fluorouracil | - |
dc.subject | DNA, Neoplasm | - |
dc.subject | Deoxycytidine | - |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | - |
dc.subject | Prognosis | - |
dc.subject | Mutation | - |
dc.subject | Genes, ras | - |
dc.subject | Adult | - |
dc.subject | Aged | - |
dc.subject | Aged, 80 and over | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.subject | Phosphatidylinositol 3-Kinases | - |
dc.subject | Class I Phosphatidylinositol 3-Kinases | - |
dc.subject | Antibodies, Monoclonal, Humanized | - |
dc.subject | Bevacizumab | - |
dc.subject | Capecitabine | - |
dc.title | 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 | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1038/bjc.2015.37 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Price, T. [0000-0002-3922-2693] | - |
dc.identifier.orcid | Hardingham, J. [0000-0001-8277-1199] | - |
dc.identifier.orcid | Townsend, A. [0000-0003-3563-4719] | - |
dc.identifier.orcid | Wrin, J. [0000-0003-3584-7343] | - |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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