ESMO @ ECC 2013: Addition of Trebananib to Paclitaxel Significantly Increases Progression-free Survival in Women with Recurrent Epithelial Ovarian Cancer

The results from phase III study of trebananib, an anti-angiogenesis peptibody.

The first reported findings from the phase III TRINOVA-1 trial evaluating trebananib plus paclitaxel versus placebo plus paclitaxel in women with recurrent epithelial ovarian cancer showed that the trial met its primary endpoint of improving progression-free survival (PFS). Although data for overall survival (OS) are not yet mature, a promising trend towards improved OS was observed at an interim analysis.

Taken together with an overall good safety profile, trebananib may offer an alternative treatment option in the near future to women with epithelial epithelial ovarian cancer who, for the most part, present with advanced disease; approximately 80% of these women will experience recurrence and eventually die from their disease.

Findings from the late-breaking abstract were presented on 1 October during the Gynaecological Cancer Proffered Papers Session (Abstract E17-7107) at the 17th ECCO – 38th ESMO – 32nd ESTRO European Cancer Congress. The European Cancer Congresses are organised in joint partnership with ESSO, EACR, EONS and SIOPE as a forum for the latest in oncology research and to offer multidisciplinary and multi-professional educational opportunities in oncology. The 2013 Congress convened in Amsterdam, The Netherlands from 27 September until 01 October.

Anti-angiogenesis strategy by inhibiting binding of angiopoietin 1/2 to the Tie2 receptor

Dr. Bradley Monk of the Department of Obstetrics and Gynecology, Creighton University School of Medicine and University of Arizona Cancer Center at St Joseph's Hospital, Phoenix, USA headed an international team in conducting the TRINOVA-1 study of trebananib in women with recurrent endothelial ovarian cancer. Tribananib is an anti-angiogenesis peptibody that inhibits the binding of angiopoietin 1/2 to the Tie2 receptor, thus interfering with the additional blood supply that supports oncogenesis.

TRINOVA-1 (trial identifier NCT01204749) was a phase III randomised, double-blind trial that compared paclitaxel plus trebananib to paclitaxel and placebo. The trial enrolled 919 women aged 18 years and older with measurable or evaluable recurrent epithelial ovarian cancer and adequate organ function who were stratified according to duration of platinum-free interval (PFI), measurable disease, and region and then randomised to receive paclitaxel at 80 mg/m2 i.v. weekly on a 3 weeks on/1 week off basis plus either placebo or trebananib at 15 mg/kg weekly.

Patients had received one prior front-line platinum-based regimen and were allowed to receive two additional cytotoxic regimens but patients with a PFI >12 months or who were platinum-refractory were excluded. Treatment arms were similar with regard to age, race, primary tumour site, performance status, tumour grade, and number of prior regimens. The primary endpoint was progression-free survival (PFS) and overall survival (OS) was a secondary endpoint.

The data cut-off date was March 2013. Results showed a  statistically significant difference in PFS, which was prolonged by 52% with trebananib; median PFS was 7.2 months in the trebananib arm versus 5.4 months in the control arm (hazard ratio [HR] 0.66, p < 0.001). A 34% reduction in the risk of disease progression or death was also seen. The response rate increased from 30% with placebo to 38% with trebananib.

The OS data are expected to mature in 2014 and results are anticipated then; however at an interim analysis preplanned at 313 deaths, a trend towards improved OS of median 19.0 versus 17.3 months (HR 0.86; p = 0.19) favouring trebananib over placebo was observed.

In the trebananib arm, the most frequently reported adverse events (AEs) were localised oedema, nausea and alopecia. The rate of discontinuation of investigational product due to adverse events was 20% in the trebananib arm versus 7% in the control arm.

While localised oedema was increased, the investigators noted that class-specific anti-vascular endothelial growth factor associated AEs such a hypertension, proteinuria, wound-healing complications or arterial thrombotic events were not increased with trebananib.

Based on these results, further study of trebananib is warranted and there are several ongoing trials of different formulations trebananib.

The first author reported the following conflicts of interest in term of corporate-sponsored research: he has received money for research from Amgen, but this was not paid to him directly but to his institution.