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
; 70: 111-121, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27914241
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.Palavras-chave
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Protocolos de Quimioterapia Combinada Antineoplásica
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Eur J Cancer
Ano de publicação:
2017
Tipo de documento:
Article