title: Randomized, phase II, placebo-controlled trial of onartuzumab and/or bevacizumab in combination with weekly paclitaxel in patients with metastatic triple-negative breast cancer.
abstract: BACKGROUND
  Increased hepatocyte growth factor/MET signaling is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer (TNBC). We evaluated the benefit of adding onartuzumab, a monoclonal anti-MET antibody, to paclitaxel with/without bevacizumab in patients with TNBC.
  
  
  METHODS
  Women with metastatic TNBC were randomized to receive onartuzumab plus placebo plus weekly paclitaxel (OP; n = 60) or onartuzumab plus bevacizumab plus paclitaxel (OBP; n = 63) or placebo plus bevacizumab plus paclitaxel (BP; n = 62). The primary end point was progression-free survival (PFS); additional end points included overall survival (OS), objective response rate (ORR), and safety. This trial was hypothesis generating and did not have power to detect minimum clinically meaningful differences between treatment arms.
  
  
  RESULTS
  There was no improvement in PFS with the addition of onartuzumab to BP [hazard ratio (HR), 1.08; 95% confidence interval (CI) 0.69-1.70]; the risk of a PFS event was higher with OP than with BP (HR, 1.74; 95% CI 1.13-2.68). Most patients had MET-negative tumors (88%); PAM50 subtype analysis showed basal-like tumors in 68% of samples. ORR was higher in the bevacizumab arms (OBP: 42.2%; 95% CI 28.6-57.1; BP: 54.7%; 95% CI 41.0-68.4) compared with OP (27.5%; 95% CI 15.9-40.6). Median OS was shorter with OBP (HR, 1.36; 95% CI 0.75-2.46) and OP (HR, 1.92; 95% CI 1.03-3.59), than with BP. Peripheral edema was more frequent in the onartuzumab arms (OBP, 51.8%; OP, 58.6%) versus BP (17.7%).
  
  
  CONCLUSIONS
  This study did not show a clinical benefit of the addition of onartuzumab to paclitaxel with/without bevacizumab in patients with predominantly MET-negative TNBC.
  
  
  BACKGROUND
  NCT01186991.
authors.affiliation: Department of Clinical Research, Institut Curie Paris & Saint Cloud, Paris. Electronic address: veronique.dieras@curie.fr.
authors.forename: V
authors.initials: V
authors.lastname: Diéras
authors.affiliation: Centre René Gauducheau, Centre Régional de Lutte Contre le Cancer (CRLC) Nantes, Atlantique, France.
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.affiliation: Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Yardley
authors.affiliation: Institut du Cancer de Montpellier (ICM), Montpellier, France.
authors.forename: G
authors.initials: G
authors.lastname: Romieu
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: V
authors.initials: V
authors.lastname: Valero
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: S J
authors.initials: SJ
authors.lastname: Isakoff
authors.affiliation: Genentech, Inc., South San Francisco, USA.
authors.forename: H
authors.initials: H
authors.lastname: Koeppen
authors.affiliation: Genentech, Inc., South San Francisco, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Wilson
authors.affiliation: Genentech, Inc., South San Francisco, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Genentech, Inc., South San Francisco, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Shames
authors.affiliation: Genentech, Inc., South San Francisco, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mocci
authors.affiliation: Roche Product Development, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Schmid
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos / Q000627:therapeutic use; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D010919:Placebos; D000068258:Bevacizumab; C584058:onartuzumab; D017239:Paclitaxel
keywords: MET; bevacizumab; onartuzumab; paclitaxel; phase II; triple-negative breast cancer