alpelisib + fulvestrant + ribociclib

This is a combination regimen of three drugs used in oncology research and clinical trials for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. - **Alpelisib** is a selective inhibitor of the phosphatidylinositol-3-kinase alpha isoform (PI3Kα), targeting tumors with activating PIK3CA mutations. - **Fulvestrant** is an estrogen receptor antagonist that binds to and degrades the estrogen receptor, blocking estrogen signaling in breast cancer cells. - **Ribociclib** is a cyclin-dependent kinase 4/6 inhibitor that blocks cell cycle progression by inhibiting CDK4/6-mediated phosphorylation of the retinoblastoma protein. The rationale for combining these agents lies in dual pathway inhibition—targeting both PI3K and CDK4/6 pathways along with endocrine therapy—to overcome resistance mechanisms and improve outcomes in HR+/HER2– breast cancer. While doublet combinations such as alpelisib plus fulvestrant or ribociclib plus fulvestrant are approved and widely used, triple therapy has been explored in early-phase clinical trials but was limited by toxicity concerns[1][7]. No recommended phase II dose was established for this triple combination due to unexpected toxicity[1].

Brand names

Piqray (alpelisib)Kisqali (ribociclib)Faslodex (fulvestrant)

Other names

alpelisib + fulvestrant + ribociclib