Final survival results of the randomized phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer.

Abstract

5046 Background: Trabectedin (T) in combination with pegylated liposomal doxorubicin (PLD) was demonstrated to improve progression-free survival (PFS) and overall response rate (ORR) in comparison to PLD alone as a second-line treatment of recurrent ovarian cancer (J Clin Oncol 28:3107-14, 2010). We report the protocol defined final analysis of overall survival (OS). Methods: Women ≥18 years, stratified by performance status (0-1 vs 2) and platinum-free interval (PFI) <6 vs > 6 months(m), were randomly assigned to receive an IV infusion of PLD 30 mg/m2 followed by a 3-hour infusion of T 1.1 mg/m2 every 3 weeks or PLD 50 mg/m2 every 4 weeks. The primary endpoint was PFS by independent radiology assessment and secondary endpoints included OS and ORR. Results: The final OS analysis was performed on 12 Nov 2010. The median follow-up was 47.4m. Among the 672 randomized subjects, 522 (77.7%) deaths were observed (258 in the T+PLD arm and 264 in the PLD arm). The median OS for T+PLD and PLD arms was 22.2 and 18.9m, respectively (HR= 0.86; 95%CI: 0.72, 1.02; p=0.0835 [unstratified log-rank test]). There was an unanticipated imbalance in the PFI between the two arms favoring the PLD arm (mean PFI: PLD=13.3m, T+D=10.6m. To provide a better estimate of the true treatment effect of adding T to PLD, a multivariate analysis adjusted for key prognostic factors (including PFI) was performed which demonstrated a significant improvement in OS in subjects treated with the combination (HR=0.82; 95%CI: 0.69,0.98; p=0.0285). Consistent improvement in OS was seen across all PFI subgroups, which was more pronounced in 6-12PFI subgroup (Table). Conclusions: T+PLD combination showed an improvement in OS in recurrent ovarian cancer compared with PLD alone. Randomized trials of T+PLD versus platinum combinations are indicated. Subgroup analysis by PFI. Subgroup by PFI (m) Median PLD (m) Median T+PLD (m) HR (95%CI) 0-6 12.3 14.2 0.94 (0.71, 1.25) 6-12 16.4 22.4 0.64 (0.47, 0.86) >12 31.7 36.5 0.83 (0.59, 1.16)