Opsalin: A phase II placebo (Pbo)-controlled randomized study of ombrabulin in patients with platinum-sensitive recurrent ovarian cancer (OC) treated with carboplatin (Cb) and paclitaxel (P).

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Abstrakt byl publikován rovněž v Supplementu časopisu
J Clin Oncol 31, 2013 (suppl; abstr 5516)

Abstract:

Background: Patients with platinum-sensitive recurrent OC are often retreated with CbP due to limited treatment options. Ombrabulin (AVE8062), a combretastatin A4 analog, is a vascular disrupting agent that damages established tumor vasculature causing tumor necrosis and has synergistic antitumor activity with platinum agents in vivo (Cancer Sci. 2003;94:200). OPSALIN evaluated whether adding ombrabulin to CbP improves outcomes in patients with platinum-sensitive recurrent OC (NCT01332656; EFC10260). Methods: Patients (aged ≥18 yrs, ECOG PS ≤2) with platinum-sensitive measurable ovarian, fallopian tube, or primary peritoneum carcinoma after completion of one line of platinum-based chemotherapy received ombrabulin 35 mg/m² or Pbo plus CbP (AUC 5–6, 175 mg/m²) every 3 weeks. Randomization (1:1) was stratified by time of first disease recurrence (6–12 or >12 months). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate (RR), and safety. An interim analysis after ~54 PFS events (60% of the target 90 PFS events) was planned. Results: From May 2011 to August 2012, 154 patients were randomized (n=77 in each group). Groups were balanced in terms of baseline characteristics. Overall, the median age was 56 yrs (range 34–79), 93% had ovarian primary tumors, and 54% had first disease recurrence >12 months. Planned interim analysis was performed after 53 PFS events (27 ombrabulin; 26 Pbo); median follow-up was 6.8 months. Ombrabulin did not improve PFS vs Pbo in any subgroup (global median 8.4 vs 10.4 months, respectively; HR 1.33; 60%CI 1.06–1.69). Overall, RR was 65% for ombrabulin and 71% for Pbo. Safety profiles were comparable; rates of grade 3–4 adverse events were 51% for ombrabulin and 41% for Pbo, with no particular safety signals. Conclusions: This interim analysis has suggested no safety concerns or efficacy advantage of adding ombrabulin to CbP in patients with platinum-sensitive recurrent OC. The study was discontinued due to limited probability of the ombrabulin arm showing PFS superiority at the final analysis. Study sponsored by Sanofi. Clinical trial information: NCT01332656.