title: Efficacy of bevacizumab and chemotherapy in the first-line treatment of metastatic colorectal cancer: broadening KRAS-focused clinical view.
abstract: BACKGROUND
  The aim of the present retrospective study was to analyze clinical outcome and risk factors associated with treatment outcomes according to KRAS status in patient with metastatic colorectal cancer (mCRC) treated with bevacizumab (bev) plus chemotherapy in the first-line setting.
  
  
  METHODS
  We performed observational study on 1622 patients with mCRC treated with bev plus oxaliplatin- or irinotecan-based chemotherapy, and correlated treatment outcomes with KRAS mutation status. The primary endpoint was progression-free survival (PFS) and additionally overall survival (OS). Adverse events of bevacizumab and risk factors including location of metastases were evaluated.
  
  
  RESULTS
  Mutation in KRAS was present in 40.6% of mCRC cases. The median PFS in patients with wild-type KRAS (wtKRAS) vs mutant KRAS was 11.5 vs 11.4 months, respectively. The median OS was 30.7 vs 28.4 months (p = 0.312). Patients with KRAS mutation had lung metastases more frequently than wtKRAS individuals (32.0% vs 23.8%; p = 0.001). We observed no difference in clinical outcome between hepatic and extrahepatic metastatic disease.
  
  
  CONCLUSIONS
  KRAS mutation does not interfere with clinical benefit from first-line treatment with bevacizumab plus chemotherapy in mCRC patients.
authors.affiliation: Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. bencsikova@mou.cz.|Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic. bencsikova@mou.cz.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Bencsikova
authors.affiliation: Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic. bortlicek@iba.muni.cz.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Bortlicek
authors.affiliation: Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. jana.halamkova@mou.cz.
authors.forename: Jana
authors.initials: J
authors.lastname: Halamkova
authors.affiliation: Department of Internal Medicine and Hematooncology, University Hospital Brno, Brno, Czech Republic. lenka.ostrizkova@fnbrno.cz.
authors.forename: Lenka
authors.initials: L
authors.lastname: Ostrizkova
authors.affiliation: Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. kiss@mou.cz.|Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic. kiss@mou.cz.
authors.forename: Igor
authors.initials: I
authors.lastname: Kiss
authors.affiliation: Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic. bohuslav.melichar@fnol.cz.
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Melichar
authors.affiliation: Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic. pavlik@iba.muni.cz.
authors.forename: Tomas
authors.initials: T
authors.lastname: Pavlik
authors.affiliation: Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic. dusek@iba.muni.cz.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Dusek
authors.affiliation: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic. valik@mou.cz.|Department of Laboratory Medicine, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 656 53, Czech Republic. valik@mou.cz.
authors.forename: Dalibor
authors.initials: D
authors.lastname: Valik
authors.affiliation: Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. vyzula@mou.cz.|Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic. vyzula@mou.cz.|Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic. vyzula@mou.cz.
authors.forename: Rostislav
authors.initials: R
authors.lastname: Vyzula
authors.affiliation: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic. dubska@mou.cz.|Department of Laboratory Medicine, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 656 53, Czech Republic. dubska@mou.cz.|Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. dubska@mou.cz.
authors.forename: Lenka
authors.initials: L
authors.lastname: Zdrazilova-Dubska
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D000077150:Oxaliplatin; D010071:Oxaloacetates; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin