6533b862fe1ef96bd12c6f0f

RESEARCH PRODUCT

Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

Eduardo Díaz-rubioAuxiliadora Gómez-españaBartomeu MassutíJavier SastreMargarita ReboredoJosé Luis ManzanoFernando RiveraM José SafontClara MontagutEncarnación GonzálezManuel BenavidesEugenio MarcuelloAndrés CervantesPurificación Martínez De PradoCarlos Fernández-martosAntonio ArriviInmaculada BandoEnrique ArandaSpanish Cooperative Group For The Treatment Of Digestive Tumors (Ttd)

subject

MaleOncologyOrganoplatinum Compoundsendocrine system diseasesEpidemiologyColorectal cancer:Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings]DeoxycytidineMetastasis:Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]Antineoplastic Combined Chemotherapy ProtocolsPathologyMedicineNeoplasm Metastasisgeneslcsh:Sciencemediana edad:Analytical Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols [Medical Subject Headings]Aged 80 and overanciano:Chemicals and Drugs::Organic Chemicals::Organometallic Compounds::Organoplatinum Compounds [Medical Subject Headings]Cancer Risk FactorsClinical Pharmacologyprotocolos de quimioterapia antineoplásica combinadaColon AdenocarcinomaPronósticoCombination chemotherapyadultoPrognosisBevacizumabOxaliplatinpronósticoOncologyMedicineOncology Agentsmedicine.medical_specialty:Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings]FluorouraciloBevacizumab:Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 1-Ring::Pyrimidines::Pyrimidine Nucleosides::Cytidine::Deoxycytidine [Medical Subject Headings]:Check Tags::Male [Medical Subject Headings]Molecular GeneticsCapecitabine:Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies Monoclonal::Antibodies Monoclonal Humanized [Medical Subject Headings]Gastrointestinal TumorsGenetics:Named Groups::Persons::Age Groups::Adult [Medical Subject Headings]HumansClinical TrialsBiologyneoplasmsCapecitabineAgedlcsh:R:Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings]:Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes Neoplasm::Oncogenes::Proto-Oncogenes::Genes ras [Medical Subject Headings]medicine.diseasedigestive system diseasesOxaliplatin:Check Tags::Female [Medical Subject Headings]PharmacogeneticsMutationlcsh:QfluorouraciloMultivariate analysisDesoxicitidinahumanosCancer Treatment:Named Groups::Persons::Age Groups::Adult::Aged::Aged 80 and over [Medical Subject Headings]lcsh:Medicinemedicine.disease_causeNeoplasias colorrectalesSurgical oncologyBasic Cancer Research:Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 1-Ring::Pyrimidines::Pyrimidinones::Uracil::Fluorouracil [Medical Subject Headings]Clinical Trials (Cancer Treatment)metástasis neoplásicaMetástasis neoplásicaMultidisciplinaryMiddle AgedGenetic EpidemiologyProtocolos de quimioterapia antineoplásica combinadaFemaleAntiangiogenesis TherapyFluorouracilKRASColorectal NeoplasmsResearch Articlemedicine.drugAdultDrugs and DevicesClinical Pathologyneoplasias colorrectalesClinical Research DesignGenetic Causes of CancerAntibodies Monoclonal HumanizedAntibodiesRectal CancerAntibody TherapyDiagnostic MedicineInternal medicine:Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis [Medical Subject Headings]:Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings]mutaciónClinical GeneticsMutaciónbusiness.industryPharmacoepidemiologyCancers and NeoplasmsHuman GeneticsChemotherapy and Drug TreatmentdesoxicitidinaGenes rasanticuerposGenetics of Diseasebusinesscompuestos organoplatino

description

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.

yearjournalcountryeditionlanguage
2012-10-12PLoS ONE
https://doi.org/10.1371/journal.pone.0047345