Statistical analysis
REGRESSION, EVENTS, ADVERSE EVENTS
This trial was designed as a superiority study to assess OS in patients receiving the trabectedin/PLD doublet compared with those receiving the reference carboplatin/PLD doublet. The primary hypothesis was that median OS would range between 18 and 24 months in the reference arm on the basis of previously published results and that the trabectedin/PLD doublet would improve median OS by 6–8 months (Hazard Ratio [HR] = 0.75). Assuming a one-sided α of 0.025 and β 0.15 and loss to follow-up 5%, it was calculated that 442 events were needed. Considering an accrual period of 42 months and a follow-up of about 30 months, the trial was planned to recruit 588 patients.A one-sided α test was chosen because the positive effect of TFIp with trabectedin/PLD was deemed probable, and we were not interested in proving the superiority of the standard treatment.We compared survival outcomes between treatment groups using a log-rank test. We estimated the HR and 95% CI for survival outcomes for treatment comparisons using a Cox regression model adjusted for the randomisation stratification factors. We used the Kaplan–Meier method to estimate the median PFS and OS for the two treatment groups.Differences between arms in adverse events were tested with a χ2 test for trend.For each treatment group, the mean difference between the two time-points of the EORTC QLQ-C30 and EORTC QLQ-OV28 subscales is presented and differences between arms were tested by means Efficacy analyses were done for patients randomly assigned in the trial according to their original treatment assignment and with no major violations (i.e. intention-to-treat [ITT] population). Safety analyses were done for patients who received at least one chemotherapy cycle.The IDMC reviewed unblinded safety data on a periodic basis, the results of the futility interim analysis and efficacy interim analysis. The Sponsor trial management staff, clinicians and funder were blinded to the efficacy results until the final analysis of OS.Statistical analyses were done in SAS (version 9.4).The study is registered with ClinicalTrials.gov, number NCT01379989 and European Clinical Trials database, EudraCT 2010-022949-17.