A Randomized, Double-Blind, Placebo (Pbo)-Controlled Phase Iii Study Of Ombrabulin Plus Cisplatin In Patients (Pts) With Advanced-Stage Soft-Tissue Sarcoma After Failure Of Anthracycline And Ifosfamide Chemotherapies.

10506 Background: Ombrabulin (AVE8062) is a vascular disrupting agent that damages established tumor vasculature and has demonstrated synergistic antitumor activity with cisplatin in vivo. In a phase I study, ombrabulin 25 mg/m² plus cisplatin 75 mg/m² was identified as the recommended dose in pts with solid tumors (AACR 2008; Abs 08-AB-4925). This phase III study evaluated the efficacy and safety of ombrabulin plus cisplatin in pts with advanced soft-tissue sarcoma (NCT00699517). Methods: Pts (aged ≥18 yrs, ECOG PS ≤2) with metastatic soft-tissue sarcoma who had received prior anthracycline and ifosfamide, with ≤2 prior chemotherapies for advanced disease, were randomized (1:1) to receive either ombrabulin 25 mg/m² or Pbo plus cisplatin 75 mg/m² every 3 weeks. The primary objective was to compare progression-free survival (PFS) between arms; secondary objectives included overall survival (OS) and safety. Results: Overall, 355 pts (median age 52 yrs; 51.5% male) were randomized (176 ombrabulin, 179 Pbo) in 44 centers worldwide. Median duration of follow-up was 27.9 and 30.5 months in Pbo and ombrabulin arms, respectively. PFS analysis showed a statistically significant improvement with ombrabulin (median 1.54 vs 1.41 months Pbo; HR=0.76, 95% CI 0.59–0.98; p=0.0302), with 3- and 6-month rates in favor of ombrabulin vs Pbo: 35.4% vs 24.9% and 19.3% vs 10.6%, respectively. A trend for an improvement with ombrabulin was observed in 3 of the 4 prespecified histology strata: liposarcoma, leiomyosarcoma, and “other”, but not for pleomorphic. Analysis of OS did not show statistically significant improvement with ombrabulin (median 11.43 vs 9.33 months Pbo, HR=0.85, 95% CI 0.67–1.09). OS rates at 1 year were in favor of ombrabulin (48.6% vs 42.4% Pbo). Grade 3/4 TEAEs more frequently seen with ombrabulin included neutropenia (19.2% vs 7.9% Pbo) and thrombocytopenia (8.5% vs 3.4% Pbo). Conclusions: Although this trial met its primary efficacy endpoint, the combination of ombrabulin and cisplatin did not demonstrate sufficient clinical benefit in pts with advanced soft-tissue sarcoma to warrant further study. Clinical trial information: NCT00699517.