CAPItello-291 Study Design and Intermittent Capivasertib Dosing

Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute, reviews the design of CAPItello-291, a phase 3, double-blind, placebo-controlled trial in hormone receptor positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer after endocrine progression, allowing up to 2 prior endocrine lines and 1 prior chemotherapy, requiring a majority of patients to have received a prior cyclin-dependent kinase (CDK) 4/6 inhibitor, permitting hemoglobin A1c up to 8%, and enrolling without biomarker selection. Patients were randomized to capivasertib 400 mg twice daily on a 4-days-on, 3-days-off schedule plus fulvestrant or placebo plus fulvestrant, with dual primary progression-free survival endpoints. Sarah L. Sammons, MD, of the University of Maryland Greenebaum Comprehensive Cancer Center, calls the fulvestrant-only comparator appropriate then but outdated now. Seth A. Wander, MD, PhD, of Massachusetts General Hospital, attributes the intermittent schedule to toxicity mitigation, trading a more complex calendar for a better therapeutic index.