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

Giovanni Scambia, Domenica Lorusso, Christian Marth, Ignace Vergote, Willi Oberaigner, Andrew Clamp, Regina Berger, Christian Kurzeder, Nicoletta Colombo, Peter Vuylsteke, Marcia Hall, Vincent Renard, Sandro Pignata, Rebecca Kristeleit, Sevilay Altintas, Gordon Rustin, Robert M. Wenham, Mansoor Raza Mirza, Peter C. Fong, Amit OzaBradley J. Monk, Haijun Ma, Florian D. Vogl, Bruce A. Bach

Risultato della ricerca: Contributo in rivistaArticolo in rivista

45 Citazioni (Scopus)

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/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. 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
Lingua originaleEnglish
pagine (da-a)111-121
Numero di pagine11
RivistaEuropean Journal of Cancer
Volume70
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • Adult
  • Aged
  • Angiogenesis Inhibitors
  • Antibiotics, Antineoplastic
  • Antineoplastic Combined Chemotherapy Protocols
  • Cancer Research
  • Disease-Free Survival
  • Double-Blind Method
  • Doxorubicin
  • Duration of response
  • ENGOT-ov-6/TRINOVA-2
  • Female
  • Humans
  • Middle Aged
  • Objective response rate
  • Oncology
  • Ovarian Neoplasms
  • Pegylated liposomal doxorubicin
  • Platinum
  • Polyethylene Glycols
  • Progression-free survival
  • Recombinant Fusion Proteins
  • Trebananib

Fingerprint

Entra nei temi di ricerca di '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'. Insieme formano una fingerprint unica.

Cita questo