Statistical analysis
SECONDARY
The primary endpoint (and secondary pharmacodynamic endpoints) were analyzed in the modified intent-to-treat (mITT) population, which included all randomized study participants who took at least one dose of randomized study medication and had both baseline and post-treatment (centrally assessed) Ki67 values. Safety and tolerability were analyzed in the safety population, which included all randomized study participants who took at least one dose of study medication. Pharmacokinetic variables were analyzed in the pharmacokinetic-evaluable population, which included all participants who received at least one dose of amcenestrant and had at least one evaluable post-treatment plasma concentration. As a result of early termination of trial enrollment, no formal statistical inferences were conducted; only descriptive statistics were provided.Sample size calculations showed that 40 evaluable participants (i.e., with both baseline and post-treatment Ki67 values) per treatment arm would be needed to achieve 85% marginal power, assuming a geometric mean of reduction of 70% for letrozole and 85% for amcenestrant, and a standard deviation of 1 of the log-fold change at the overall one-sided type I error rate of 2.5% controlled with the Hochberg procedure, based on a one-sided Changes in Ki67 were analyzed using a geometric least-squares mean (LSM) approach. Geometric LSMs of the proportional change in Ki67 were based on an analysis of covariance (ANCOVA) model for the log-proportional change on treatment, with treatment and log-transformed Ki67 at baseline as fixed effects, and converted by antilog transformation. The geometric LSM of relative reduction (with 95% confidence interval [CI]) was defined as 1 − geometric LSM of the proportional change.The proportion of participants with a relative decrease from baseline in Ki67 ≥ 50% was reported using descriptive statistics, and the Clopper-Pearson method was used to calculate the 95% CI. For absolute change in ER H-score from baseline, geometric LSMs (with 95% CIs) were based on an ANCOVA model for the change on treatment, with treatment and ER H-score at baseline as fixed effects. Relative change from baseline in ER H-score was reported using descriptive statistics.Safety data were summarized descriptively.