title: Cetuximab could be more effective without prior bevacizumab treatment in metastatic colorectal cancer patients.
abstract: BACKGROUND
  Cetuximab and bevacizumab reportedly improve the survival of patients with metastatic colorectal cancer (mCRC), but their most effective sequence of administration is unknown. The aim of this study was to compare the survival of patients with mCRC treated with cetuximab after bevacizumab failure with that of patients with mCRC without previous bevacizumab therapy.
  
  
  METHODS
  In total, 190 of 323 patients with mCRC treated with cetuximab from March 2006 to July 2013 were enrolled in our hospital for this retrospective study. Forty-seven patients were treated with cetuximab-based second-line therapy, 21 of whom had received prior bevacizumab; 143 patients were treated with cetuximab-based third-line therapy, 109 of whom had received prior bevacizumab. The Kaplan-Meier method with a log-rank test and Cox regression analysis were performed to evaluate the overall survival and progression-free survival (PFS) of each group of patients.
  
  
  RESULTS
  The median follow-up time was 11.8 months in patients who received second-line cetuximab-based chemotherapy and 13.7 months in those who received third-line cetuximab-based chemotherapy. Univariate analysis revealed that the median PFS was significantly longer in patients without prior bevacizumab therapy than in patients with prior bevacizumab therapy (second line, P=0.048; third line, P=0.0022). Multivariate analysis adjusted for baseline characteristics showed that third-line cetuximab-based chemotherapy with or without prior bevacizumab was significantly associated with PFS (P=0.014). Neither the presence nor the absence of prior bevacizumab administration was associated with overall survival.
  
  
  CONCLUSIONS
  Cetuximab could be more effective without prior bevacizumab. Prior bevacizumab use may decrease the efficacy of cetuximab.
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsusaka
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Suenaga
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinozaki
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
keywords: EGFR; VEGF; bevacizumab; cetuximab; metastatic colorectal cancer