FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer

Eur J Cancer. 2014 Jan;50(1):57-63. doi: 10.1016/j.ejca.2013.08.024. Epub 2013 Oct 15.


Background: BRAF V600E mutation plays a negative prognostic role in metastatic colorectal cancer (mCRC), leading to a median Progression Free Survival (PFS) of 4-6months with first-line conventional treatments. Our group recently reported in a retrospective exploratory analysis of a phase II trial that FOLFOXIRI (5-FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab might allow to achieve remarkable results in terms of PFS and Overall Survival (OS) also in this poor-prognosis subgroup. The aim of this work was to prospectively validate our retrospective finding.

Patients and methods: This phase II trial was designed to detect an increase in 6month-Progression Free Rate (6m-PFR) from 45% to 80% in a population of BRAF mutant mCRC patients treated with first-line FOLFOXIRI plus bevacizumab. Secondary end-points were PFS, OS, response rate (RR) and the analysis of outcome parameters in the pooled population consisting of both retrospectively and prospectively included patients. This trial is registered with, number NCT01437618.

Results: Two-hundred-fourteen potentially eligible mCRC patients were screened for BRAF mutational status. Fifteen BRAF mutant patients (7%) were included in the validation cohort. At a median follow up of 25.7months, 6m-PFR was 73%. Median PFS and OS were 9.2 and 24.1months, respectively. In the pooled population, at a median follow up of 40.4months, 6m-PFR was 84%. Median PFS and OS were 11.8 and 24.1months, respectively. Overall RR and disease control rate were 72% and 88%, respectively.

Conclusion: Lacking randomised trials in this specific molecular subgroup, FOLFOXIRI plus bevacizumab might be a reasonable option for the first-line treatment of BRAF mutant mCRC patients.

Keywords: BRAF; Bevacizumab; Chemotherapy; Colorectal cancer; FOLFOXIRI.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics*
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Prognosis
  • Prospective Studies
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics*
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Organoplatinum Compounds
  • Bevacizumab
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • FOLFOXIRI protocol

Associated data