capivasertib + fulvestrant + palbociclib

Capivasertib + fulvestrant + palbociclib is an investigational combination therapy for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. Capivasertib is a selective AKT inhibitor that targets the PI3K/AKT signaling pathway, which is often implicated in resistance to endocrine therapy. Fulvestrant is a selective estrogen receptor degrader (SERD) that antagonizes and degrades the estrogen receptor, thereby inhibiting ER-driven tumor growth. Palbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor that blocks cell cycle progression from G1 to S phase by inhibiting CDK4 and CDK6 activity. The rationale for combining these agents stems from their complementary mechanisms of action targeting key pathways involved in HR-positive breast cancer proliferation and resistance mechanisms. This triple combination aims to overcome resistance seen with prior endocrine therapies and CDK4/6 inhibitors by simultaneously inhibiting ER signaling, cell cycle progression, and the PI3K/AKT pathway[1][2][7].