Everolimus-Exemestane for Advanced Breast Cancer

The primary efficacy analysis (progression-free survival), based on local assessment, was a log-rank test stratified according to visceral metastases and previous hormone sensitivity. A total of 528 progression-free survival events were required for the final analysis, in order to detect a hazard ratio of 0.74 with 90% power with the use of a log-rank test and a two-look Lan–DeMets group-sequential design with an O’Brien–Fleming-type boundary¹⁹ at a one-sided cumulative 2.5% level of significance. Further assuming a median progression-free survival of 3.7 months in the control group,^{6 (link)} 18 months of recruitment, a 10% rate of loss to follow-up, and a 2:1 randomization ratio in favor of the everolimus–exemestane group, 705 patients were to be randomly assigned. The study had a prespecified interim analysis after the observation of approximately 60% of the progression-free survival events (the event count was 359). At the time of the interim analysis, the data and safety monitoring committee was to disclose that the trial met its primary end point only if both analyses of progression-free survival (local and central assessments) crossed the thresholds of significance, as prospectively defined in the charter of the committee.