title: Role of Kras status in patients with metastatic colorectal cancer receiving first-line chemotherapy plus bevacizumab: a TTD group cooperative study.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Medical Oncology, Hospital Clínico San Carlos (HCSC), Red Temática de Investigación Cooperativa en Cáncer, Facultad de Medicina, Universidad Complutense, Instituto de Investigación Sanitaria del HCSC (IdISSC), Madrid, Spain. ediazrubio.hcsc@salud.madrid.org
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Auxiliadora
authors.initials: A
authors.lastname: Gómez-España
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Massutí
authors.forename: Javier
authors.initials: J
authors.lastname: Sastre
authors.forename: Margarita
authors.initials: M
authors.lastname: Reboredo
authors.forename: José Luis
authors.initials: JL
authors.lastname: Manzano
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.forename: M José
authors.initials: MJ
authors.lastname: Safont
authors.forename: Clara
authors.initials: C
authors.lastname: Montagut
authors.forename: Encarnación
authors.initials: E
authors.lastname: González
authors.forename: Manuel
authors.initials: M
authors.lastname: Benavides
authors.forename: Eugenio
authors.initials: E
authors.lastname: Marcuello
authors.forename: Andrés
authors.initials: A
authors.lastname: Cervantes
authors.forename: Purificación
authors.initials: P
authors.lastname: Martínez de Prado
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Martos
authors.forename: Antonio
authors.initials: A
authors.lastname: Arrivi
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Bando
authors.forename: Enrique
authors.initials: E
authors.lastname: Aranda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil