Díaz-Rubio, EduardoGómez-España, AuxiliadoraMassutí, BartomeuSastre, JavierReboredo, MargaritaManzano, José LuisRivera, FernandoSafont, M JoséMontagut, ClaraGonzález, EncarnaciónBenavides, ManuelMarcuello, EugenioCervantes, AndrésMartínez de Prado, PurificaciónFernández-Martos, CarlosArrivi, AntonioBando, InmaculadaAranda, Enrique2013-10-182013-10-182012-10-12Díaz-Rubio E, Gómez-España A, Massutí B, Sastre J, Reboredo M, Manzano JL, et al. Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study. PLoS ONE. 2012; 7(10):e47345http://hdl.handle.net/10668/1333Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't;BACKGROUND In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. METHODOLOGY/PRINCIPAL FINDINGS KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64). CONCLUSIONS/SIGNIFICANCE This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.enNeoplasias colorrectalesDesoxicitidinaFluorouraciloMutaciónMetástasis neoplásicaPronósticoProtocolos de quimioterapia antineoplásica combinadaMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::AgedMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and overMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, HumanizedMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy ProtocolsMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal NeoplasmsMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidine Nucleosides::Cytidine::DeoxycytidineMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Uracil::FluorouracilMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Neoplasm::Oncogenes::Proto-Oncogenes::Genes, rasMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm MetastasisMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Organometallic Compounds::Organoplatinum CompoundsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Organometallic Compounds::Organoplatinum CompoundsMedical Subject Headings::Named Groups::Persons::Age Groups::Adultresearch article23174912open access10.1371/journal.pone.00473451932-6203PMC3470549