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

Eur J Cancer. 2017 Jan;70:111-121. doi: 10.1016/j.ejca.2016.09.004. Epub 2016 Dec 1.

Abstract

Aims: 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.

Methods: Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m2 once 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.

Results: 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%).

Conclusions: 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.

Trial registration: ClinicalTrials.gov, NCT01281254.

Keywords: Duration of response; ENGOT-ov-6/TRINOVA-2; Objective response rate; Pegylated liposomal doxorubicin; Progression-free survival; Trebananib.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Disease-Free Survival
  • Double-Blind Method
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives
  • Female
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Platinum / therapeutic use
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects

Substances

  • Angiogenesis Inhibitors
  • Antibiotics, Antineoplastic
  • Recombinant Fusion Proteins
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Platinum
  • Doxorubicin
  • trebananib

Associated data

  • ClinicalTrials.gov/NCT01281254