Poster Spotlight Session 12: Putting Brakes on the Cell Cycle: Understanding Mechanisms Governing CDK 4/6 inhibitor Resistance and Role for Novel Therapeutic Strategies
Thursday, December 7 • 7:00 a.m. – 8:00 a.m. • Stars at Night Ballroom 1-2

Presentation: Capivasertib plus cyclin-dependent kinase 4/6 inhibitor and fulvestrant in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: updated Phase 1b analysis from CAPItello-292

Barbara Pistilli, MD
Gustave Roussy,
Villejuif, France

What is your presentation about?
Capivasertib is a potent inhibitor of all three AKT isoforms. Previously, the Phase 3 CAPItello-291 trial (NCT04305496) showed that in patients with HR-positive/HER2-negative advanced breast cancer who progressed on endocrine therapy, the addition of capivasertib to fulvestrant compared with placebo plus fulvestrant resulted in statistically significant and clinically meaningful improvement in progression-free survival. A clinically meaningful benefit was observed in patients with or without prior CDK4/6 inhibitor exposure.

Our presentation is about the CAPItello-292 Phase 1b trial (NCT04862663) assessing the safety and efficacy of combining capivasertib with a CDK4/6 inhibitor (palbociclib or ribociclib) and fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer. Based on a previous preliminary analysis, the recommended Phase 3 dose of capivasertib plus palbociclib and fulvestrant was determined. In this presentation, we report updated results for the palbociclib combination, including safety and tolerability and preliminary signals of clinical activity (tumor response and circulating tumor DNA dynamics).

What makes this topic important in 2023?
Since activation of the PI3K/AKT pathway is implicated in resistance to endocrine therapy and CDK4/6 inhibitors, simultaneously inhibiting the PI3K/AKT and CDK4/6 pathways may delay CDK4/6 inhibitor resistance and/or re-sensitize tumors to endocrine therapy plus CDK4/6 inhibition, leading to improved clinical outcomes.

Recruitment is ongoing into the Phase 3 component of CAPItello-292 (NCT04862663), an open-label, randomized trial assessing the efficacy and safety of the addition of capivasertib to fulvestrant and the investigator’s choice of CDK4/6 inhibitor (palbociclib or ribociclib) in patients with HR-positive/HER2-negative advanced breast cancer following recurrence or progression on or within 12 months of the end of (neo)adjuvant endocrine therapy.