Ibrance (Palbociclib) for Advanced Breast Cancer - Initial Clinical Guidance Report

The trial was initially designed as a phase 1/2 trial with the intention of using Cohort 1 as an exploratory analysis of efficacy and safety, while the primary analysis was intended for Cohort 2. The accrual to Cohort 2 was stopped after an unplanned interim analysis of Cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of Cohorts 1 and 2 (instea [...] In the interim, based on the results of PALOMA-1, it is possible the use of letrozole in the adjuvant setting for ER+ post-menopausal women may decrease, as prior use of letrozole will be a barrier to receiving the combination of letrozole and palbociclib in the advanced treatment setting. [...] The selection and sequencing of these therapies depend on the biological characteristics of the breast cancer, tumour burden, involvement of vital organs, pace of the disease, performance status, comorbidities of the patient, and patient preference. [...] Due to the number of data-driven amendment changes, as well as the open-label design and small sample size of the trial, the FDA requested the trial sponsor conduct a blinded independent central review (BICR) of the PFS data. [...] The multiple data-driven amendment changes compromised the statistical plan of the trial and cast doubt on the integrity of the obtained results and the magnitude of the reported treatment effect estimates.