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

British Journal of Cancer
T J PriceNiall C Tebbutt

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...Continue Reading

References

Oct 12, 2004·Hematology/oncology Clinics of North America·Lee M Ellis
May 24, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Herbert I HurwitzFairooz Kabbinavar
Jul 7, 2005·Journal of the National Cancer Institute·William L InceHartmut Koeppen
Mar 5, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rafael G AmadoDavid D Chang
Apr 19, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Leonard B SaltzJim Cassidy
Oct 24, 2008·The New England Journal of Medicine·Christos S KarapetisJohn R Zalcberg
Jul 15, 2009·Advances in Cancer Research·Bing-Hua Jiang, Ling-Zhi Liu
Oct 10, 2009·The Journal of Molecular Diagnostics : JMD·Vicki WhitehallBarry Iacopetta
Jun 3, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Niall C TebbuttTimothy J Price
Jan 14, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C BokemeyerP Koralewski
Apr 20, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric Van CutsemFortunato Ciardiello
Jun 8, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Timothy J PriceNiall C Tebbutt
Oct 4, 2011·Cancer Genetics·Pedro PintoManuel R Teixeira
Feb 24, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiaoyun LiaoShuji Ogino
Aug 29, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John MoroneyRazelle Kurzrock
Dec 4, 2012·Oncology Letters·Yinxu ZhangChunying Liu
May 2, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fiona L DayOliver M Sieber
Sep 13, 2013·The New England Journal of Medicine·Jean-Yves DouillardScott D Patterson
Sep 18, 2013·The Journal of Experimental Medicine·Adriana SolerBart Vanhaesebroeck
Nov 13, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christos S KarapetisUNKNOWN NCIC Clinical Trials Group and the Australasian Gastro-Intestinal Trials Group
Oct 1, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Carrie A ThompsonBrian K Link
Oct 3, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jennifer A LigibelClifford A Hudis

❮ Previous
Next ❯

Citations

Aug 28, 2016·Surgical Oncology·Sean M Ronnekleiv-KellyTimothy M Pawlik
Aug 6, 2016·Expert Review of Molecular Diagnostics·Ian A Cree
Sep 7, 2016·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Volker HeinemannJean-Yves Douillard
Oct 17, 2017·Oncotarget·Yassine RidouaneBenjamin Haaland
Mar 25, 2016·Expert Review of Anticancer Therapy·Timothy J PriceJeremy D Shapiro
Feb 13, 2018·World Journal of Gastroenterology : WJG·A-Jian LiLu Yin
Jun 21, 2020·Journal of Cancer Research and Clinical Oncology·Arndt StahlerDominik Paul Modest
Nov 23, 2019·International Journal of Molecular Sciences·Apostolos PapachristosGregory B Sivolapenko
Aug 23, 2020·Cancers·Federica MarmorinoChiara Cremolini
Jan 29, 2019·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J VidalC Montagut
May 22, 2021·Journal of Chemotherapy·Fahima Danesh PouyaMohadeseh Nemati
Jun 15, 2021·Seminars in Oncology·Sally TemrazAli Shamseddine
Mar 17, 2021·Journal of the National Comprehensive Cancer Network : JNCCN·Al B BensonLisa A Gurski

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.