Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12672
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.
Authors: Price, Timothy J;Bruhn, M A;Lee, C K;Hardingham, J E;Townsend, A R;Mann, K P;Simes, J;Weickhardt, A;Wrin, J W;Wilson, K;Gebski, V;Van Hazel, G;Robinson, B;Cunningham, D;Tebbutt, Niall C
Affiliation: 1] Haematology-Oncology Department, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia [2] School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia.
School of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
NHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW 2050, Australia.
1] Haematology-Oncology Department, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia [2] School of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
Haematology-Oncology Department, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia.
Sir Charles Gardiner Hospital, Perth, WA, Australia.
Christchurch Hospital, Christchurch, New Zealand.
Royal Marsden Hospital, London, UK.
1] Austin Health, Heidelberg, VIC 3084, Australia [2] Ludwig Institute for Cancer Research, Heidelberg, VIC 3084, Australia.
Issue Date: 17-Mar-2015
Citation: British Journal of Cancer 2015; 112(6): 963-70
Abstract: 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.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.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.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.
Internal ID Number: 25742472
URI: http://ahro.austin.org.au/austinjspui/handle/1/12672
DOI: 10.1038/bjc.2015.37
URL: http://www.ncbi.nlm.nih.gov/pubmed/25742472
Type: Journal Article
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.