Impact of trebananib plus weekly paclitaxel on overall survival (OS) in patients (pts) with recurrent ovarian cancer and ascites: Results from the phase III TRINOVA-1 study.

5503 Background: Trebananib is an antiangiogenic peptibody that inhibits angiopoietin 1 and 2 binding to the Tie2 receptor. TRINOVA-1 showed significantly longer progression-free survival (PFS) in the trebananib arm (Monk et al, Lancet Oncol 2014;15:799). We evaluated OS, including clinically important subgroups, and postprogression PFS (PFS2). Methods: 919 women with recurrent epithelial ovarian cancer (platinum-free interval < 12 mo) were randomized to paclitaxel (P) 80 mg/m2 IV QW (3 wks on/1 wk off) plus either blinded trebananib 15 mg/kg IV QW (T+P) or placebo (P alone). Treatment continued until progression, toxicity or consent withdrawal. PFS was the primary, intent to treat (ITT) OS a key secondary endpoint. Exploratory PFS2 analysis followed the EMA guidance (EMA/CHMP/27994/2008/Rev.1; 13 Dec 2012). Results: After median follow-up of 17.7 mo and 628 OS events, median OS (ITT) was 19.3 mo with T+P vs 18.3 mo with P alone (HR = 0.95, 95% CI, 0.81–1.11; p = 0.55). Prespecified subgroup analysis of OS also evaluated 295 (32%) pts with ascites at baseline. Characteristics did not differ between pts with and without ascites, and pts with ascites randomized to T+P vs P alone. There was a difference in median OS of 2.2 mo between pts with ascites receiving T+P vs P alone (14.5 vs 12.3 mo; HR = 0.72, 95% CI 0.55–0.93; p = 0.011). After on-study progression, 684 (74%) pts received a median of 2 (range, 1–8) additional lines of therapy. Median PFS2 in the T+P arm increased by 1.6 mo (12.5 vs 10.9 mo with P alone; HR = 0.85, 95% CI 0.74–0.98; p = 0.024). Analysis of time to second subsequent therapy confirmed the PFS2 result (median 13.4 vs 11.7 mo with P alone; HR = 0.83, 95% CI, 0.72–0.96; p = 0.012). The incidence of grade ≥ 3 adverse events (AEs) was 60% for T+P vs 56% for P alone. T+P was associated with more AE-related treatment discontinuations (22% vs 8%) and localized edema events (any grade, 59% vs 27%). Conclusions: Despite multiple additional lines of therapy, OS was longer with T+P among pts with ascites but not in the ITT population (no decrement). The initially reported PFS benefit was sustained through next subsequent anticancer therapy, translating into longer PFS2. Clinical trial information: NCT01204749.

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