Trebananib in Platinum-Sensitive Ovarian Cancer

A new antiangiogenesis inhibitor with a different mechanism of action than bevacizumab shows promise in platinum-sensitive ovarian cancer, according to results of the phase 3 TRINOVA-1 trial presented at the 2013 meeting of the European Cancer Congress. Trebananib added to paclitaxel prolonged the time to disease progression or death by 52% compared with paclitaxel plus placebo (P <.001), said Bradley Monk, MD, Creighton University School of Medicine and University of Arizona Cancer Center, Phoenix.

Although angiogenesis is a proven target in ovarian cancer, anti–vascular endothelial growth factor (VEGF) therapy (with bevacizumab) causes adverse effects. Trebananib is a different approach, targeting a non-VEGF angiogenesis factor—angiopoietin 1 and angiopoietin 2. The hope is that this approach will be effective and have fewer adverse effects than a VEGF-targeted strategy, Monk said.

TRINOVA-1 enrolled 919 women with recurrent epithelial ovarian cancer and randomized them to receive treatment with weekly intravenous (IV) trebananib 15 mg/kg plus weekly IV paclitaxel (3 weeks on, 1 week off) or with placebo plus weekly paclitaxel (3 weeks on, 1 week off). Patients were treated until disease progression, toxicity, or withdrawal of consent.

Patients were stratified according to progression-free interval, measurable disease, and geographic region. At baseline, patients had received up to 3 prior cytotoxic regimens and had a progression-free interval of <12 months. One prior regimen failed in 40% of patients, 2 prior therapies in 40%, and 3 prior therapies in 20%.

Monk presented primary progression-free survival (PFS) and interim overall survival (OS) results of this international trial. At a median follow-up of 10 months, median PFS was 7.2 months in the trebananib group and 5.4 months for placebo (hazard ratio, 0.66; 95% confidence interval, 0.56-0.76; P <.001).

A prespecified subgroup analysis found that trebananib improved PFS in all subgroups. Overall response rate was 38% with trebananib versus 30% with placebo (most were partial responses).

Trebananib did not appear to increase toxicity when added to paclitaxel, according to the safety analysis. The rate of adverse events of any grade was similar between the 2 treatment arms: 96% for trebananib and 97% for placebo. The major toxicity of trebananib was edema: 57% versus 26% (any grade) for those in the placebo arm. Very few grade ≥3 adverse events were reported with trebananib. No increase in VEGF-associated adverse effects was seen with trebananib (ie, hypertension, proteinuria, wound healing complications, arterial thrombotic events).

Neutropenia and anemia were more common in the placebo arm, and neurotoxicity was more common in the trebananib arm, which may be attributable to increased exposure to paclitaxel in that arm.

An interim OS analysis showed a difference of approximately 2 months favoring trebananib (19 months vs 17.3 months for the placebo arm), but this is only a preliminary analysis, Monk reminded listeners.

TRINOVA-1 incorporated patient-reported outcomes using 3 different quality-of-life questionnaires: Functional Assessment of Cancer Therapy-Ovarian (FACT-O), Ovarian Cancer Screening (OCS), and EuroQol 5-dimension (EQ-5D). On these measures, no quality-of-life differences were reported between the 2 treatment arms.

Trebananib is continuing to be developed for ovarian cancer.

The formal discussant of this trial, Antonio Casado, MD, Hospital Universitario San Carlos, Madrid, Spain, said, “Weekly paclitaxel and trebananib could be an option in patients who progress within 12 months after 1 to 3 previous lines of therapy.”

Reference

Monk BJ, Poveda A, Vergote I, et al. A phase III, randomized, double-blind trial of weekly paclitaxel plus the angiopoietin 1 and 2 inhibitor, trebananib, or placebo in women with recurrent ovarian cancer: TRINOVA-1. Presented at: 2013 European Cancer Congress; September 27-October 1, 2013; Amsterdam, the Netherlands. Abstract LBA41.