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|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  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  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  Ludwig Institute for Cancer Research, Heidelberg, VIC 3084, Australia.
|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|
|Appears in Collections:||Journal articles|
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