Literature DB >> 21960311

The influence of KRAS and BRAF mutations on the efficacy of cetuximab-based first-line therapy of metastatic colorectal cancer: an analysis of the AIO KRK-0104-trial.

D P Modest1, A Jung, N Moosmann, R P Laubender, C Giessen, C Schulz, M Haas, J Neumann, S Boeck, T Kirchner, V Heinemann, S Stintzing.   

Abstract

Our study investigated the impact of specific KRAS mutations and BRAF mutation on progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated within the AIO KRK-0104-trial as first-line therapy. In total, 146 (of 185) patients were included in this analysis. Seventy-nine patients presented with KRAS/BRAF wild-type (wt), 41 patients with a KRAS codon 12 and nine patients with a KRAS codon 13 mutation. Seventeen patients presented a BRAF-mutated tumor. The patients of our study were treated with CAPIRI/CAPOX plus cetuximab. Major differences regarding PFS and OS were observed depending on the mutation of the tumor. PFS was 8 months in patients with wt-tumors, 5.8 months with codon 12-mutated, 9.9 months with codon 13-mutated and 4.2 months with BRAF-mutated tumors. OS was 23.5 months in patients with wt-tumors, 18.9 months with codon 12-mutated, 26.2 months with codon 13-mutated and 13.0 months with BRAF-mutated tumors. Although the conventional separation of patients with KRAS wild-type versus KRAS mutant tumors did not have a significant impact on outcome parameters in the AIO KRK 0104-trial, this analysis demonstrates that markedly differing results are obtained when subtypes of KRAS and BRAF mutation are taken into account.
Copyright © 2011 UICC.

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Year:  2011        PMID: 21960311     DOI: 10.1002/ijc.26467

Source DB:  PubMed          Journal:  Int J Cancer        ISSN: 0020-7136            Impact factor:   7.396


  19 in total

Review 1.  [Molecular pathology of colorectal cancer].

Authors:  J H L Neumann; A Jung; T Kirchner
Journal:  Pathologe       Date:  2015-03       Impact factor: 1.011

2.  Mutation-specific RAS oncogenicity explains NRAS codon 61 selection in melanoma.

Authors:  Christin E Burd; Wenjin Liu; Minh V Huynh; Meriam A Waqas; James E Gillahan; Kelly S Clark; Kailing Fu; Brit L Martin; William R Jeck; George P Souroullas; David B Darr; Daniel C Zedek; Michael J Miley; Bruce C Baguley; Sharon L Campbell; Norman E Sharpless
Journal:  Cancer Discov       Date:  2014-09-24       Impact factor: 39.397

3.  A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer.

Authors:  Robin M J M van Geel; Josep Tabernero; Elena Elez; Johanna C Bendell; Anna Spreafico; Martin Schuler; Takayuki Yoshino; Jean-Pierre Delord; Yasuhide Yamada; Martijn P Lolkema; Jason E Faris; Ferry A L M Eskens; Sunil Sharma; Rona Yaeger; Heinz-Josef Lenz; Zev A Wainberg; Emin Avsar; Arkendu Chatterjee; Savina Jaeger; Eugene Tan; Kati Maharry; Tim Demuth; Jan H M Schellens
Journal:  Cancer Discov       Date:  2017-03-31       Impact factor: 39.397

4.  Effect of BRAF V600E mutation on tumor response of anti-EGFR monoclonal antibodies for first-line metastatic colorectal cancer treatment: a meta-analysis of randomized studies.

Authors:  Dandan Cui; Dan Cao; Yu Yang; Meng Qiu; Ying Huang; Cheng Yi
Journal:  Mol Biol Rep       Date:  2014-01-04       Impact factor: 2.316

5.  Repurposing EGFR Inhibitor Utility in Colorectal Cancer in Mutant APC and TP53 Subpopulations.

Authors:  Mingli Yang; Michael J Schell; Andrey Loboda; Michael Nebozhyn; Jiannong Li; Jamie K Teer; W Jack Pledger; Timothy J Yeatman
Journal:  Cancer Epidemiol Biomarkers Prev       Date:  2019-04-23       Impact factor: 4.254

6.  Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian carcinoma.

Authors:  Gian Franco Zannoni; Giuseppina Improta; Gaia Chiarello; Angela Pettinato; Marco Petrillo; Paolo Scollo; Giovanni Scambia; Filippo Fraggetta
Journal:  Virchows Arch       Date:  2014-06-03       Impact factor: 4.064

7.  The prognostic role of BRAF mutation in metastatic colorectal cancer receiving anti-EGFR monoclonal antibodies: a meta-analysis.

Authors:  Zi-Xu Yuan; Xiao-Yan Wang; Qi-Yuan Qin; De-Feng Chen; Qing-Hua Zhong; Lei Wang; Jian-Ping Wang
Journal:  PLoS One       Date:  2013-06-11       Impact factor: 3.240

8.  High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort.

Authors:  Halfdan Sorbye; Anca Dragomir; Magnus Sundström; Per Pfeiffer; Ulf Thunberg; Monica Bergfors; Kristine Aasebø; Geir Egil Eide; Fredrik Ponten; Camilla Qvortrup; Bengt Glimelius
Journal:  PLoS One       Date:  2015-06-29       Impact factor: 3.240

Review 9.  Colorectal Cancer: From Genetic Landscape to Targeted Therapy.

Authors:  Mouade El Bali; Joaira Bakkach; Mohcine Bennani Mechita
Journal:  J Oncol       Date:  2021-07-06       Impact factor: 4.375

10.  Biomarkers of benefit from cetuximab-based therapy in metastatic colorectal cancer: interaction of EGFR ligand expression with RAS/RAF, PIK3CA genotypes.

Authors:  George Pentheroudakis; Vassiliki Kotoula; Wendy De Roock; George Kouvatseas; Pavlos Papakostas; Thomas Makatsoris; Demetris Papamichael; Ioannis Xanthakis; Joseph Sgouros; Despina Televantou; Georgia Kafiri; Athanassios C Tsamandas; Evangelia Razis; Eleni Galani; Dimitrios Bafaloukos; Ioannis Efstratiou; Iliada Bompolaki; Dimitrios Pectasides; Nicholas Pavlidis; Sabine Tejpar; George Fountzilas
Journal:  BMC Cancer       Date:  2013-02-02       Impact factor: 4.430

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