Assuming an enrollment rate of 50 patients per month (20 months to complete enrollment) and study duration of approximately 64 months, a total sample size of approximately 1000 patients was planned. Statistical methods All time-to-event endpoints were analysed using Kaplan-Meier methods to estimate survival distributions and the median time-to-event. For rPFS and OS the treatments were compared using the stratified log rank test. Only one analysis of rPFS was planned, after 378 events. Three interim analyses and one final analysis of the OS endpoint were planned, after 116, 311, 425 and 773 events (corresponding to approximately 15%, 40%, 55% and 100% of the total events). The first interim analysis was scheduled for the same time as the rPFS analysis. The purpose of the interim analyses was to terminate the study if superiority of abiraterone was demonstrated. O’Brien-Fleming stopping boundaries, incorporating an alpha-spending function were used. Subgroup analyses were conducted for both rPFS and OS with the HR within each subgroup estimated using a non-stratified Cox proportional hazard model. Various sensitivity analyses were also planned, including investigator-assessed rPFS. The secondary endpoints were analysed using the Hochberg test procedure, with the overall level of significance controlled at the 2-tailed, 0.05 level. Analyses of other endpoints did not include adjustments for multiplicity for multiple comparisons. Each endpoint was tested at a 2-tailed 0.05 level of significance. Participant flow A total of 1,088 subjects were randomised and 1,082 received treatment. At the 20 December 2011 cut-off date 31% of patients in the abiraterone arm and 16% of subjects in the placebo arm were still receiving treatment. A flow diagram for the study is shown in Figure 1. Reasons for discontinuation are shown in Table 4 and Table 5. Figure 1:Pivotal study 302 - Participant flow and analysis sets. Table 4: Pivotal study 302 Discontinuations – Table 5: Pivotal study 302 Discontinuations due to unequivocal clinical progression – Major protocol violations/deviations Major protocol violations are shown in Table 6. These were balanced between treatment arms. Table 6: Pivotal study 302 Major protocol violations – Baseline data Baseline data indicate that the two groups were well matched at baseline. The groups were also well matched with respect to baseline BPI-SF pain scores and analgesic use.
Assuming an enrollment rate of 50 patients per month (20 months to complete enrollment) and study duration of approximately 64 months, a total sample size of approximately 1000 patients was planned. Statistical methods All time-to-event endpoints were analysed using Kaplan-Meier methods to estimate survival distributions and the median time-to-event. For rPFS and OS the treatments were compared using the stratified log rank test. Only one analysis of rPFS was planned, after 378 events. Three interim analyses and one final analysis of the OS endpoint were planned, after 116, 311, 425 and 773 events (corresponding to approximately 15%, 40%, 55% and 100% of the total events). The first interim analysis was scheduled for the same time as the rPFS analysis. The purpose of the interim analyses was to terminate the study if superiority of abiraterone was demonstrated. O’Brien-Fleming stopping boundaries, incorporating an alpha-spending function were used. Subgroup analyses were conducted for both rPFS and OS with the HR within each subgroup estimated using a non-stratified Cox proportional hazard model. Various sensitivity analyses were also planned, including investigator-assessed rPFS. The secondary endpoints were analysed using the Hochberg test procedure, with the overall level of significance controlled at the 2-tailed, 0.05 level. Analyses of other endpoints did not include adjustments for multiplicity for multiple comparisons. Each endpoint was tested at a 2-tailed 0.05 level of significance. Participant flow A total of 1,088 subjects were randomised and 1,082 received treatment. At the 20 December 2011 cut-off date 31% of patients in the abiraterone arm and 16% of subjects in the placebo arm were still receiving treatment. A flow diagram for the study is shown in Figure 1. Reasons for discontinuation are shown in Table 4 and Table 5. Figure 1:Pivotal study 302 - Participant flow and analysis sets. Table 4: Pivotal study 302 – Discontinuations Table 5: Pivotal study 302 – Discontinuations due to unequivocal clinical progression Major protocol violations/deviations Major protocol violations are shown in Table 6. These were balanced between treatment arms. Table 6: Pivotal study 302 – Major protocol violations Baseline data Baseline data indicate that the two groups were well matched at baseline. The groups were also well matched with respect to baseline BPI-SF pain scores and analgesic use.
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