Final Overall Survival Results in the Intention-to-Treat Population

Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute, reviews final overall survival in the overall population of CAPItello-291, the phase 3 trial of capivasertib plus fulvestrant in hormone receptor positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Because the PIK3CA/AKT1/PTEN-altered analysis was not significant, overall survival was not formally tested here; the hazard ratio was 1.00 with medians of roughly 29 months in both arms, forest plots consistent across subgroups, and the same imbalance in subsequent targeted therapy favoring the control arm. Seth A. Wander, MD, PhD, of Massachusetts General Hospital, says the result does not change his view, describing an ongoing debate over how much pathway alterations matter for AKT inhibition, citing contradictory signals from translational work and trials such as FAKTION, and noting all-comers approvals in some countries, though he finds biomarker-selected use more biologically sensible while newer options emerge for unaltered disease.