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

• Published in: European journal of cancer (1990) 2017-01, Vol.70, p.111-121
• Main Authors: Marth, Christian, Vergote, Ignace, Scambia, Giovanni, Oberaigner, Willi, Clamp, Andrew, Berger, Regina, Kurzeder, Christian, Colombo, Nicoletta, Vuylsteke, Peter, Lorusso, Domenica, Hall, Marcia, Renard, Vincent, Pignata, Sandro, Kristeleit, Rebecca, Altintas, Sevilay, Rustin, Gordon, Wenham, Robert M, Mirza, Mansoor Raza, Fong, Peter C, Oza, Amit, Monk, Bradley J, Ma, Haijun, Vogl, Florian D, Bach, Bruce A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Angiopoietin; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - adverse effects; Anticancer properties; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor activity; Ascites; Cancer; Clinical trials; Disease-Free Survival; Double-Blind Method; Double-blind studies; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Doxorubicin - analogs & derivatives; Duration of response; Edema; ENGOT-ov-6/TRINOVA-2; Fc receptors; Female; Fusion protein; Hazards; Health hazards; Hematology, Oncology and Palliative Medicine; Humans; Intravenous administration; Middle Aged; Objective response rate; Ovarian cancer; Ovarian Neoplasms - drug therapy; Patients; Pegylated liposomal doxorubicin; Platinum; Platinum - therapeutic use; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - adverse effects; Progression-free survival; Protein-tyrosine kinase receptors; Randomization; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - adverse effects; Shortages; Trebananib; Tyrosine; Vomiting; Women; Womens health
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2016.09.004

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