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

Marth, C., Vergote, I., Scambia, G., Oberaigner, W., Clamp, A., Berger, R., et al. (2017). 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. EUROPEAN JOURNAL OF CANCER, 70, 111-121 [10.1016/j.ejca.2016.09.004].

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

COLOMBO, NICOLETTA;
2017

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
Articolo in rivista - Articolo scientifico
Duration of response; ENGOT-ov-6/TRINOVA-2; Objective response rate; Pegylated liposomal doxorubicin; Progression-free survival; Trebananib; Oncology; Cancer Research
English
111
121
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Marth, C., Vergote, I., Scambia, G., Oberaigner, W., Clamp, A., Berger, R., et al. (2017). 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. EUROPEAN JOURNAL OF CANCER, 70, 111-121 [10.1016/j.ejca.2016.09.004].
Marth, C; Vergote, I; Scambia, G; Oberaigner, W; Clamp, A; Berger, R; Kurzeder, C; Colombo, N; Vuylsteke, P; Lorusso, D; Hall, M; Renard, V; Pignata, S; Kristeleit, R; Altintas, S; Rustin, G; Wenham, R; Mirza, M; Fong, P; Oza, A; Monk, B; Ma, H; Vogl, F; Bach, B
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/139508
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