Highlights
- •Trebananib + PLD did not meet the primary end-point of improving PFS.
- •However, trebananib + PLD improved objective response rate and duration of response.
- •No new safety signals were identified in the ENGOT-ov-6/TRINOVA-2 study.
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
Keywords
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Article info
Publication history
Published online: December 02, 2016
Accepted:
September 1,
2016
Received in revised form:
August 26,
2016
Received:
June 24,
2016
Footnotes
Research support: This work was funded by Amgen Inc.
Identification
Copyright
© 2016 Published by Elsevier Ltd.
