Abstract Aim Trabectedin in combination with pegylated liposomal doxorubicin (PLD) improves progression-free survival (PFS) compared to PLD alone in recurrent ovarian cancer (J Clin Oncol 2010;28:3107–14). Methods Women, stratified by performance status (0–1 versus 2) and platinum sensitivity (platinum-free interval PFI <6 versus ⩾6 months), were randomly assigned to receive PLD 30 mg/m2 IV followed by a 3-h infusion of trabectedin 1.1 mg/m2 every 3 weeks or PLD 50 mg/m2 every 4 weeks. The study was powered to show a 33% increase in overall survival (OS) after 520 deaths had occurred. Results After a median follow-up of 47.4 months, there were 522 deaths among 672 subjects. The median OS for trabectedin + PLD and PLD arms was 22.2 and 18.9 months, respectively (hazard ratio HR = 0.86; 95% confidence interval CI: 0.72–1.02; p = 0.0835). An unexpected but significant imbalance in the PFI favouring the PLD arm (mean PFI: PLD = 13.3 months, trabectedin + PLD = 10.6 months) was identified. On the basis of this finding, an unplanned hypothesis generating analysis adjusting for the PFI imbalance and other prognostic factors suggested an improvement in OS associated with the trabectedin + PLD arm (HR = 0.82; 95% CI: 0.69–0.98; p = 0.0285). In another unplanned exploratory analysis, the subset of patients with a PFI of 6–12 months had the largest difference in OS (HR = 0.64; 95% CI: 0.47–0.86; p = 0.0027). Conclusions The final OS analysis did not meet the protocol-defined criterion for statistical significance. Despite stratification on platinum sensitivity, there was an imbalance in mean platinum free interval that had an effect on OS.