title: Prognostic value of the combination of circulating tumor cells plus KRAS in patients with metastatic colorectal cancer treated with chemotherapy plus bevacizumab.
abstract: OBJECTIVE
  Circulating tumor cells (CTCs) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) status were identified as prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab in analyses of the MACRO (Maintenance Treatment in Advanced Colorectal Cancer) trial. In this post hoc analysis of the MACRO trial, the potential additive effect of these 2 factors on patient outcomes was explored.
  
  
  METHODS
  A total of 158 of the 480 patients involved in the MACRO trial were included in the biological marker substudy. CTC isolation and enumeration were centralized and performed using the CellSearch System (Veridex LLC, Raritan, NJ) in 7.5 mL of whole blood. Evaluation of KRAS status was performed retrospectively by the standard method used at each center. PFS and OS were analyzed by the Kaplan-Meier method according to CTC count and KRAS status.
  
  
  RESULTS
  Patients with < 3 CTC per 7.5 mL blood at baseline and KRAS wild-type tumors had a median PFS of 14.2 months compared with 6.2 months in patients with ≥ 3 CTCs and KRAS mutated tumors (P < .0001; hazard ratio, 3.0; 95% confidence interval, 1.8-5.2). Similar findings were observed for OS (28.9 and 13.7 months, respectively, P = .0004; hazard ratio 2.8; 95% confidence interval, 1.6-4.9). Multivariate analyses showed that CTC count ≥ 3 and KRAS status were the only independent prognostic factors for both PFS and OS.
  
  
  CONCLUSIONS
  This post hoc analysis showed that CTC count and KRAS status were independent prognostic factors for outcomes in patients with metastatic colorectal cancer treated with bevacizumab ± chemotherapy. These factors should be taken into account in the design of future phase III trials.
authors.affiliation: Medical Oncology Department, HC San Carlos, Madrid, Spain (Center affiliated with the Red Temática de Investigación Cooperativa (RD06/0020/0021), Instituto Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain). Electronic address: jsastre.hcsc@salud.madrid.org.
authors.forename: Javier
authors.initials: J
authors.lastname: Sastre
authors.forename: Marta
authors.initials: M
authors.lastname: Vidaurreta
authors.forename: Auxiliadora
authors.initials: A
authors.lastname: Gómez
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Massutí
authors.forename: Margarita Reboredo
authors.initials: MR
authors.lastname: López
authors.forename: Albert
authors.initials: A
authors.lastname: Abad
authors.forename: Manuel
authors.initials: M
authors.lastname: Gallen
authors.forename: Manuel
authors.initials: M
authors.lastname: Benavides
authors.forename: Enrique
authors.initials: E
authors.lastname: Aranda
authors.forename: Eduardo Díaz
authors.initials: ED
authors.lastname: Rubio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis*; 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; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010071:Oxaloacetates; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D010071:Oxaloacetates; D011518:Proto-Oncogene Proteins; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D005472:Fluorouracil
keywords: Bevacizumab; Capecitabine; Circulating tumor cells; Colorectal cancer; KRAS status; Oxaliplatin; Prognostic factors