519P - FOLFOXIRI + bevacizumab (BEV) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC): Final survival and pharmacogenomic p...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Alexander Stein
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors A. Stein1, D. Atanackovic2, J. Stoehlmacher3, B. Hildebrandt4, P. Stübs5, C. Steffens6, W. Brugger7, G. Hapke8, G. Illerhaus9, E. Bluemner10, C. Bokemeyer11
  • 1University Cancer Center Hamburg Department Of Oncology/haematology, University Medical Center Hamburg-Eppendorf, 20246 - Hamburg/DE
  • 2Division Of Hematology And Hematologic Malignancies, University of Utah, 84112 - Salt Lake City/US
  • 3Tumorgenetik Bonn, Kooperation für Tumordiagnostik, 5311 - Bonn/DE
  • 4Klinik Mit Schwerpunkt Hämatologie Und Onkologie, Charite, DE-13353 - Berlin/DE
  • 5Department Of General, Visceral And Vascular Surgery, Otto-von-Guericke University Magdeburg, Magdeburg/DE
  • 6Dep. For Oncology/hematology, MVZ Haematologie/Onkologie Klinik Dr. Hancken, Stade/DE
  • 7Hematology/oncology, Schwarzwald Baar Klinikum Villingen-Schwenning, DE-78050 - Villingen-Schwenningen/DE
  • 8Dep. For Oncology/hematology, Marienkrankenhaus, Hamburg/DE
  • 9Dep. For Oncology/hematology, Klinikum Stuttgart, Stuttgart/DE
  • 10Biostatistics, ECRON ACUNOVA, Munich/DE
  • 11Dept. Hemato/oncology, UKE II. Medizinische Klinik und PoliklinikMedizinische Klinik II., 20246 - Hamburg-Eppendorf/DE



The addition of BEV to standard doublet chemotherapy (CT) improves outcomes vs CT alone in pts with mCRC. Use of more intensive triplet CT may prolong overall survival (OS), progression-free survival (PFS), increase response rates and improve resectability rates but at the expense of greater toxicity. The OPAL study examined the effect of BEV + FOLFOXIRI on PFS in pts with previously untreated unresectable mCRC. Here we report final survival and pharmacogenetic results.


Eligible pts had histologically confirmed mCRC, ECOG PS ≤1 and were 18–70 years old. Pts received ≤12 cycles of FOLFOXIRI (infusional 5-fluorouracil [FU] 3200 mg/m2, folinic acid [FA] 200 mg/m2, oxaliplatin 85 mg/m2 and irinotecan 165 mg/m2) + BEV 5 mg/kg q2w (induction phase) followed by ≤40 cycles of 5-FU/FA + BEV q2w (maintenance phase). PFS was the primary endpoint; secondary endpoints included OS, proportion of pts achieving resectability, safety, and prognostic value of pharmacogenetic profiling (single nucleotide polymorphisms (SNP) for VEGF-A, VEGFR 1-3, PDGFR beta, HIF 1 alpha, Neuropilin).


96 pts were enrolled. Of these, 90 received study medication and formed the safety population: 64 male, 26 female; median age 58 (range 28–71) years; ECOG performance status 0/1 in 49/41 pts; liver only disease in 35 pts. During induction phase a median number of 9.5 cycles FOLFOXIRI and BEV was administered. Relative dose intensities were 81-86% for all 4 drugs. The incidence of adverse events (AEs) was as previously reported and there were no new safety signals. during induction phase. In total, 61 serious AEs occurred in 34 pts (38%). AEs resulting in death occurred in 3 pts (3%); these were not considered treatment-related by the investigators. Median PFS was 11.1 months (m) (95% CI 9.4-12.0) and OS was 32.2m (95% CI 22.6-36.9). 52 pts were pharmacogenetically profiled and VEGFR 2 SNP 305 was associated with OS (CC–12.4m, CT–18.7m, and TT–30.1m; p = 0.038).


FOLFOXIRI + BEV was feasible in this mCRC pt population. Survival was relevantly increased compared to standard three drug combinations in a molecularly unstratified pt population. VEGFR 2 SNPs might be prognostic for treatment with FOLFOXIRI + BEV.


A. Stein: Roche: membership on an advisory board, corporate-sponsored research. C. Bokemeyer: Roche: corporate-sponsored research. All other authors have declared no conflicts of interest.