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Addition of Antiangiogenic Agent to First-Line Carboplatin/Paclitaxel in Ovarian Cancer


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In a phase III trial (TRINOVA-3/ENGOT-ov2/GOG- 3001) reported in The Lancet Oncology, Ignace Vergote, PhD, and colleagues found that addition of the antiangiogenic agent trebananib to carboplatin/ paclitaxel did not improve progression-free survival in first-line treatment of advanced ovarian cancer.

Ignace Vergote, PhD

Ignace Vergote, PhD

Trebananib is a peptibody that acts on the angiopoietin pathway—which is distinct from the VEGF pathway—to neutralize the interaction between Ang1 and Ang2 and the tyrosine kinase receptor Tie2.

Study Details

The double-blind trial included 1,015 women from 206 sites in 14 countries with International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers. Patients were randomly assigned 2:1 between January 2012 and February 2014 to receive first-line trebananib plus carboplatin/ paclitaxel (n = 678) or placebo plus carboplatin/paclitaxel (n = 337). Patients received six cycles of paclitaxel (175 mg/m2) and carboplatin (area under the curve = 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance with trebananib or placebo continued for up to 18 additional months.

The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population.

Progression-Free Survival

Median follow-up was 27.4 months. Median progression-free survival was 15.9 months in the trebananib group vs 15.0 months in the placebo group (hazard ratio [HR] = 0.93, P = .36).

Data on overall survival in the intention-to-treat population were not mature at data cutoff; estimated median overall survival was 46.6 months vs 43.6 months (HR = 0.99, 95% confidence interval = 0.79–1.25).

Adverse Events

Grade ≥ 3 adverse events occurred in 76% of the trebananib group vs 71% of the placebo group, with the most common being neutropenia (35% vs 38%), anemia (11% vs 12%), and leukopenia (12% vs 10%). Serious adverse events occurred in 40% vs 31% of patients. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis) and two were considered related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events were reported in the placebo group.

The investigators concluded, “Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population.”

Vergote I, et al: Lancet Oncol 20:862-876, 2019.


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