title: Metastatic colorectal cancer first-line treatment with bevacizumab: the impact of K-ras mutation.
abstract: BACKGROUND
  Bevacizumab plus chemotherapy prolongs progression-free survival (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC). Although there is strong evidence to suggest that the mutational status of the K-ras oncogene has a role as a predictive factor for activity in patients treated with cetuximab and panitumumab, few data have been obtained in patients treated with bevacizumab. We conducted an additional retrospective analysis to investigate the prognostic value of K-ras mutation relative to mCRC first-line treatment with bevacizumab.
  
  
  METHODS
  A total of 108 patients were retrospectively reviewed. K-ras status was assessed in the overall population by sequencing. Statistical association for PFS and OS was analyzed using the Kaplan-Meier method, and the prognostic role of K-ras was determined using the logrank test.
  
  
  RESULTS
  Median PFS was 10 months both for patients with wild-type (WT) K-ras and mutated (MT) K-ras (hazard ratio [HR] 0.94, P=0.75); neither difference in median OS was significant (27 months WT K-ras versus 26 months MT K-ras, HR 0.92; P=0.70). A further analysis was carried out in the two groups according to metastatic sites. No statistically significant difference in terms of PFS and OS was demonstrated between WT K-ras and MT K-ras with liver metastases only and in those with extrahepatic disease.
  
  
  CONCLUSIONS
  Although further study is required, our results seem to confirm that K-ras mutation does not have a prognostic role in mCRC patients receiving first-line treatment with bevacizumab.
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy ; Oncology Unit, ICOT Hospital, Latina, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Rossi
authors.affiliation: Oncology Unit, SM Goretti Hospital, Latina, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Veltri
authors.affiliation: Gastroenterology and Digestive Endoscopy Unit, Nuovo Regina Margherita Hospital, Rome, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Zullo
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Zoratto
authors.affiliation: Oncology Unit, Don Luigi di Liegro Hospital, Gaeta, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Colonna
authors.affiliation: Oncology Unit, Umberto I Policlinico di Roma Hospital, Sapienza University of Rome, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Longo
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.affiliation: Biostatistics and Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Department of Pathology, Sapienza University of Rome, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ruco
authors.affiliation: Oncology Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Oncology Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Romiti
authors.affiliation: Oncology Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
authors.forename: Viola
authors.initials: V
authors.lastname: Barucca
authors.affiliation: Department of Pathology, Umberto I Policlinico di Roma Hospital, Sapienza University of Rome, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Bianchi
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
authors.forename: Silverio
authors.initials: S
authors.lastname: Tomao
keywords: K-ras; bevacizumab; extrahepatic disease; liver metastases; metastatic colorectal cancer; prognostic factor