title: Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2.
abstract: OBJECTIVE
  Trebananib, a peptibody that blocks binding of angiopoietin-1 and -2 to Tie2, significantly prolonged progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer in the phase 3 TRINOVA-1 study. We report overall survival (OS) in the intent-to-treat population and clinically relevant subgroups and time to second disease progression (PFS-2).
  
  
  METHODS
  Women with recurrent disease (platinum-free interval<12months) were randomized to receive intravenous paclitaxel 80mg/m(2) (3weeks on/1week off) plus intravenous trebananib 15mg/kg or placebo, weekly. OS in the intent-to-treat population was a key secondary endpoint. Exploratory analysis of PFS-2 was conducted according to guidance by the European Medicines Agency.
  
  
  RESULTS
  Median OS was not significantly improved with trebananib compared with placebo (19.3 versus 18.3months; HR, 0.95; 95% CI, 0.81-1.11; P=0.52) in the intent-to-treat population (n=919). In subgroup analysis, trebananib improved median OS compared with placebo (14.5 versus 12.3months; HR, 0.72; 95% CI, 0.55-0.93; P=0.011) in patients with ascites at baseline (n=295). In the intent-to-treat population, trebananib significantly improved median PFS-2 compared with placebo (12.5 versus 10.9months; HR, 0.85; 95% CI, 0.74-0.98; P=0.024). The incidence and type of adverse events in this updated analysis was consistent with that described in the primary analysis; no new safety signals were detected.
  
  
  CONCLUSIONS
  OS was not significantly longer in the intent-to-treat population, although there was an improvement in OS in patients with ascites receiving trebananib. PFS-2 confirmed that the PFS benefit associated with trebananib was maintained through the second disease progression independent of the choice of subsequent therapy.
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. Electronic address: bradley.monk@chw.edu.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.affiliation: Area Clinica de Oncologia Ginecológica, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Poveda
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Leuven, Leuven Cancer Institute, KU Leuven, European Union, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Gynecologic Oncology Unit, Fondazione IRCCS, Istituto Nazionale per la Cura e lo Studio dei Tumori, Milano, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Raspagliesi
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka-Shi, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, South Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Bae
authors.affiliation: Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Oaknin
authors.affiliation: Université Lyon-I, Centre Léon Bérard, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.affiliation: Division of Gynecologic Oncology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Provencher
authors.affiliation: Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Beth Y
authors.initials: BY
authors.lastname: Karlan
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lhommé
authors.affiliation: Academic Haematology and Oncology, Cabrini Hospital, Malvern, VIC, Australia.
authors.forename: Gary
authors.initials: G
authors.lastname: Richardson
authors.affiliation: Subdirección de Medicina Interna, Instituto Nacional de Cancerologia, Mexico City, Mexico.
authors.forename: Dolores Gallardo
authors.initials: DG
authors.lastname: Rincón
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.affiliation: Universitätsklinik für Gynäkologie und Geburtshilfe, Medizinische Universität Innsbruck, Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.affiliation: Latvian Oncology Center, Riga Eastern Clinical University Hospital, Riga, Latvia.
authors.forename: Arija
authors.initials: A
authors.lastname: Brize
authors.affiliation: Regional Cancer Institute Montpellier, Montpellier, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Fabbro
authors.affiliation: Hospital Universitario La Paz Idi-Paz, Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Redondo
authors.affiliation: Alexandra Hospital, Department of Clinical Therapeutics, National & Kapodistrian University of Athens, Athens, Greece.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
authors.affiliation: Global Biostatistical Science, 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
authors.affiliation: Department of Medicine, Princess Margaret Hospital, University of Toronto, ON, Canada.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001201:Ascites / Q000209:etiology*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011993:Recombinant Fusion Proteins; D017239:Paclitaxel; C551398:trebananib
keywords: Ascites; Overall survival; Recurrent epithelial ovarian cancer; TRINOVA-1; Time to second disease progression; Trebananib