title: Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination with FOLFOX and Bevacizumab for First-Line Metastatic Colorectal Cancer.
abstract: These negative phase II results for parsatuzumab highlight the challenges of developing an agent intended to enhance the efficacy of vascular endothelial growth factor inhibition without the benefit of validated pharmacodynamic biomarkers or strong predictive biomarker hypotheses.Any further clinical development of anti-EGFL7 is likely to require new mechanistic insights and biomarker development for antiangiogenic agents.
  
  
  
  EGFL7 (epidermal growth factor-like domain 7) is a tumor-enriched vascular extracellular matrix protein that supports endothelial cell survival. This phase II trial evaluated the efficacy of parsatuzumab (also known as MEGF0444A), a humanized anti-EGFL7 IgG1monoclonal antibody, in combination with modified FOLFOX6 (mFOLFOX6) (folinic acid, 5-fluorouracil, and oxaliplatin) bevacizumab in patients with previously untreated metastatic colorectal cancer (mCRC).
  
  
  
  One-hundred twenty-seven patients were randomly assigned to parsatuzumab, 400 mg, or placebo, in combination with mFOLFOX6 plus bevacizumab, 5 mg/kg. Treatment cycles were repeated every 2 weeks until disease progression or unacceptable toxicity for a maximum of 24 months, with the exception of oxaliplatin, which was administered for up to 8 cycles.
  
  
  
  The progression-free survival (PFS) hazard ratio was 1.17 (95% confidence interval [CI], 0.71-1.93;p= .548). The median PFS was 12 months for the experimental arm versus 11.9 months for the control arm. The hazard ratio for overall survival was 0.97 (95% CI, 0.46-2.1;p= .943). The overall response rate was 59% in the parsatuzumab arm and 64% in the placebo arm. The adverse event profile was similar in both arms.
  
  
  
  There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first-line mCRC.The Oncologist2017;22:375-e30.
authors.affiliation: Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Carbonero
authors.affiliation: UZ Leuven Oncologie, Leuven, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: van Cutsem
authors.affiliation: Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.affiliation: Medical University of Gdansk, Gdansk, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.affiliation: Birmingham Hematology Oncology Associates, LLC, Birmingham, Alabama, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Gore
authors.affiliation: Austin Health, Medical Oncology, Heidelberg, Victoria, Australia.
authors.forename: Niall
authors.initials: N
authors.lastname: Tebbutt
authors.affiliation: Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada, USA.
authors.forename: Fadi
authors.initials: F
authors.lastname: Braiteh
authors.affiliation: Hospital Universitario Vall d'Hebron, Departamento de Oncología, Barcelona, Spain.
authors.forename: Guillem
authors.initials: G
authors.lastname: Argiles
authors.affiliation: University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Zev A
authors.initials: ZA
authors.lastname: Wainberg
authors.forename: Roel
authors.initials: R
authors.lastname: Funke
authors.forename: Maria
authors.initials: M
authors.lastname: Anderson
authors.forename: Bruce
authors.initials: B
authors.lastname: McCall
authors.forename: Mark
authors.initials: M
authors.lastname: Stroh
authors.forename: Eric
authors.initials: E
authors.lastname: Wakshull
authors.forename: Priti
authors.initials: P
authors.lastname: Hegde
authors.forename: Weilan
authors.initials: W
authors.lastname: Ye
authors.forename: Daniel
authors.initials: D
authors.lastname: Chen
authors.forename: Ilsung
authors.initials: I
authors.lastname: Chang
authors.forename: Ina
authors.initials: I
authors.lastname: Rhee
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina, USA Herbert.hurwitz@duke.edu.
authors.forename: Herbert
authors.initials: H
authors.lastname: Hurwitz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage*; D002135:Calcium-Binding Proteins; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; D016228:Endothelial Growth Factors; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; C000626247:parsatuzumab; D002955:Leucovorin; D005472:Fluorouracil