A statistically significant improvement in overall survival (OS) was not seen with the combination of paclitaxel and the angiogenesis inhibitor trebananib when compared with paclitaxel alone for patients with recurrent platinum-resistant ovarian cancer.
Sean E. Harper, MD
A statistically significant improvement in overall survival (OS) was not seen with the combination of paclitaxel and the angiogenesis inhibitor trebananib when compared with paclitaxel alone for patients with recurrent platinum-resistant ovarian cancer, according to top-line findings from the phase III TRINOVA-1 study.
In an earlier analysis of TRINOVA-1, the combination of paclitaxel and trebananib demonstrated a 34% improvement in the primary endpoint of progression-free survival (PFS) and a trend toward a 14% improvement in OS. In the updated findings, the median OS was 19.3 months with trebananib versus 18.3 months with placebo. However, this 1-month improvement was not statistically significant.
Amgen, the company developing the drug, announced the updated findings in a press release. Full data from the analysis will be submitted for presentation at a future medical meeting.
"While the overall survival results of the TRINOVA-1 study are disappointing, this study is the first of three phase III trials designed to evaluate the safety and efficacy of trebananib in patients with ovarian cancer," Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a statement. "We continue to explore the potential of trebananib's novel anti-tumor mechanism of action in other cancer settings."
In the phase III study, patients were randomized to weekly paclitaxel plus trebananib (n = 461) or placebo (n = 458). Intravenous trebananib was administered at 15 mg/kg weekly. The majority of patients had progression on 1-2 prior therapies.
The median PFS was 7.2 months with trebananib versus 5.4 months with placebo (HR = 0.66; 95% CI; 0.57-0.77;P<.001). The response rate was 38% with trebananib and 30% with placebo. When data were initially presented as a late-breaking abstract at the 2013 European Cancer Congress, after a third of events, the median OS was 19.0 versus 17.3 months (HR = 0.86;P= 0.19), for trebananib and placebo, respectively.
Incidence of grade 3 or higher adverse events was similar between treatment groups (56% with trebananib vs 54% with placebo). The discontinuation rate was higher in the trebananib arm versus placebo (17% vs 6%). For trebananib versus placebo, the most common grade 3/4 adverse events were ascites (11% vs 8%), neutropenia (6% vs 9%), and abdominal pain (5% vs 5%). Edema of any grade occurred in 64% of patients treated with trebananib versus 28% with placebo.
Trebananib is an investigational anti-angiogenesis recombinant peptide that inhibits the binding of angiopoietin (Ang)-1 and -2 with the Tie2 receptor. Ang-1 and -2 are involved in vessel quality and quantity.
Trebananib continues to be explored in the phase III TRINOVA-2 and -3 studies. The TRINOVA-2 study is investigating whether the addition of trebananib to pegylated liposomal doxorubicin (PLD) improves PFS over PLD alone for patients with recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer. The TRINOVA-3 study is looking at trebananib with paclitaxel or carboplatin versus either chemotherapy agent with placebo as a first-line treatment for patients with epithelial ovarian, primary peritoneal or fallopian tube cancer.
Amgen expects initial data from the TRINOVA-2 trial in 2014 and results from the TRINOVA-3 trial are expected in 2015.