Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2.

Abstract

PURPOSE:

Trebananib, a peptibody that blocks binding of angiopoietin-1 and -2 to Tie2, significantly prolonged progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer in the phase 3 TRINOVA-1 study. We report overall survival (OS) in the intent-to-treat population and clinically relevant subgroups and time to second disease progression (PFS-2).

PATIENTS AND METHODS:

Women with recurrent disease (platinum-free interval<12months) were randomized to receive intravenous paclitaxel 80mg/m(2) (3weeks on/1week off) plus intravenous trebananib 15mg/kg or placebo, weekly. OS in the intent-to-treat population was a key secondary endpoint. Exploratory analysis of PFS-2 was conducted according to guidance by the European Medicines Agency.

RESULTS:

Median OS was not significantly improved with trebananib compared with placebo (19.3 versus 18.3months; HR, 0.95; 95% CI, 0.81-1.11; P=0.52) in the intent-to-treat population (n=919). In subgroup analysis, trebananib improved median OS compared with placebo (14.5 versus 12.3months; HR, 0.72; 95% CI, 0.55-0.93; P=0.011) in patients with ascites at baseline (n=295). In the intent-to-treat population, trebananib significantly improved median PFS-2 compared with placebo (12.5 versus 10.9months; HR, 0.85; 95% CI, 0.74-0.98; P=0.024). The incidence and type of adverse events in this updated analysis was consistent with that described in the primary analysis; no new safety signals were detected.

CONCLUSIONS:

OS was not significantly longer in the intent-to-treat population, although there was an improvement in OS in patients with ascites receiving trebananib. PFS-2 confirmed that the PFS benefit associated with trebananib was maintained through the second disease progression independent of the choice of subsequent therapy.

• Authors: Bradley J Monk, Andrés Poveda, Ignace Vergote, Francesco Raspagliesi, Keiichi Fujiwara, Duk-Soo Bae, Ana Oaknin, Isabelle Ray-Coquard, Diane M Provencher, Beth Y Karlan, Catherine Lhommé, Gary Richardson, Dolores Gallardo Rincón, Robert L Coleman, Christian Marth, Arija Brize, Michel Fabbro, Andrés Redondo, Aristotelis Bamias, Haijun Ma, Florian D Vogl, Bruce A Bach, Amit M Oza
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 143 Issue 1 Pg. 27-34 (Oct 2016) ISSN: 1095-6859 [Electronic] United States
• PMID: 27546885 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Recombinant Fusion Proteins
• Paclitaxel
• trebananib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Ascites (etiology)
• Disease-Free Survival
• Double-Blind Method
• Female
• Humans
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, mortality)
• Ovarian Neoplasms (complications, drug therapy, mortality)
• Paclitaxel (administration & dosage, adverse effects)
• Recombinant Fusion Proteins (administration & dosage, adverse effects)