title: ENGOT-ov-6/TRINOVA-2: Randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer.
abstract: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer.
  
  
  
  Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m2once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo. PFS was the primary end-point; key secondary end-points were objective response rate (ORR) and duration of response (DOR). Owing to PLD shortages, enrolment was paused for 13 months; the study was subsequently truncated.
  
  
  
  Two hundred twenty-three patients were enrolled. Median PFS was 7.6 months (95% CI, 7.2-9.0) in the trebananib arm and 7.2 months (95% CI, 4.8-8.2) in the placebo arm, with a hazard ratio of 0.92 (95% CI, 0.68-1.24). However, because the proportional hazards assumption was not fulfilled, the standard Cox model did not provide a reliable estimate of the hazard ratio. ORR in the trebananib arm was 46% versus 21% in the placebo arm (odds ratio, 3.43; 95% CI, 1.78-6.64). Median DOR was improved (trebananib, 7.4 months [95% CI, 5.7-7.6]; placebo, 3.9 months [95% CI, 2.3-6.5]). Adverse events with a greater incidence in the trebananib arm included localised oedema (61% versus 32%), ascites (29% versus 9%) and vomiting (45% versus 33%).
  
  
  
  Trebananib demonstrated anticancer activity in this phase 3 study, indicated by improved ORR and DOR. Median PFS was not improved. No new safety signals were identified.
  
  
  
  ClinicalTrials.gov, NCT01281254.
authors.affiliation: AGO-Austria and Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: Christian.MARTH@tirol-kliniken.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.affiliation: BGOG and Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven Cancer Institute, KU Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: MITO and Dipartimento per la Tutela della Salute della Donna e della Vita Nascente del Bambino e Adolescente, Policlinico Universitario Agostino Gemelli, Roma, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: AGO-Austria and Department of Clinical Epidemiology of the Tirol Kliniken Ltd., Cancer Registry of Tyrol, Innsbruck, Austria.
authors.forename: Willi
authors.initials: W
authors.lastname: Oberaigner
authors.affiliation: Department of Medical Oncology, Institute of Cancer Sciences, University of Manchester, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Clamp
authors.affiliation: AGO-Austria and Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Regina
authors.initials: R
authors.lastname: Berger
authors.affiliation: AGO-Study Group and Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte/Evang. Huyssens Stiftung/Knappschaft GmbH, Essen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kurzeder
authors.affiliation: MANGO and Istituto Europeo di Oncologia and Università Milano Bicocca, Milano, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Colombo
authors.affiliation: BGOG and Department of Medical Oncology, CHU Université Catholique de Louvain, Site Sainte Elisabeth, Namur, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Vuylsteke
authors.affiliation: MITO and Unità di Ginecologia Oncologica, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Lorusso
authors.affiliation: Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK.
authors.forename: Marcia
authors.initials: M
authors.lastname: Hall
authors.affiliation: BGOG and Department of Oncology, AZ St. Lucas, Ghent, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Renard
authors.affiliation: MITO and Department of Urology and Gynecology, Istituto Nazionale Tumori "Fondazione G. Pascale" IRCCS, Naples, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.affiliation: Department of Medical Oncology, University College London Cancer Institute, London, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kristeleit
authors.affiliation: BGOG and Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Sevilay
authors.initials: S
authors.lastname: Altintas
authors.affiliation: Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: Rustin
authors.affiliation: Department of Gynecologic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Wenham
authors.affiliation: NSGO & Department of Oncology, Rigshospitalet, København, Denmark.
authors.forename: Mansoor Raza
authors.initials: MR
authors.lastname: Mirza
authors.affiliation: Medical Oncology Department, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Fong
authors.affiliation: Department of Medicine, Princess Margaret Hospital, University of Toronto, ON, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Oza
authors.affiliation: Department of Obstetrics and Gynecology, University of Arizona Cancer Center at Dignity Health St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.affiliation: Global Development Oncology, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Haijun
authors.initials: H
authors.lastname: Ma
authors.affiliation: Global Development Oncology, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Florian D
authors.initials: FD
authors.lastname: Vogl
authors.affiliation: Global Development Oncology, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bach
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010984:Platinum / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D011993:Recombinant Fusion Proteins; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D010984:Platinum; D004317:Doxorubicin; C551398:trebananib
keywords: Duration of response; ENGOT-ov-6/TRINOVA-2; Objective response rate; Pegylated liposomal doxorubicin; Progression-free survival; Trebananib