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https://hdl.handle.net/2440/90759
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Type: | Journal article |
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 |
Author: | Price, T. Bruhn, M. Lee, C. Hardingham, J. Townsend, A. Mann, K. Simes, J. Weickhardt, A. Wrin, J. Wilson, K. Gebski, V. Van Hazel, G. Robinson, B. Cunningham, D. Tebbutt, N. |
Citation: | British Journal of Cancer, 2015; 112(6):963-970 |
Publisher: | Nature Publishing Group |
Issue Date: | 2015 |
ISSN: | 0007-0920 1532-1827 |
Statement of Responsibility: | 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 |
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. |
Keywords: | Humans Colorectal Neoplasms Mitomycin Fluorouracil DNA, Neoplasm Deoxycytidine Antineoplastic Combined Chemotherapy Protocols Prognosis Mutation Genes, ras Adult Aged Aged, 80 and over Female Male Phosphatidylinositol 3-Kinases Class I Phosphatidylinositol 3-Kinases Antibodies, Monoclonal, Humanized Bevacizumab Capecitabine |
Description: | Presented in part at the American Society of Clinical Oncology annual meeting, Chicago 31 May to 3 June 2014. |
Rights: | © 2015 Cancer Research UK |
DOI: | 10.1038/bjc.2015.37 |
Published version: | http://dx.doi.org/10.1038/bjc.2015.37 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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