alpelisib + elacestrant

Alpelisib + elacestrant is an investigational, all-oral combination therapy being studied for the treatment of estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer, particularly in patients with PIK3CA and/or ESR1 mutations. Alpelisib is a selective inhibitor of phosphatidylinositol 3-kinase alpha (PI3Kα), targeting the PI3K/AKT/mTOR pathway frequently activated in breast cancers with PIK3CA mutations. Elacestrant is a next-generation oral selective estrogen receptor degrader (SERD) that antagonizes and degrades the estrogen receptor, overcoming resistance mechanisms associated with ESR1 mutations. The combination aims to address multiple resistance pathways in hormone-receptor positive metastatic breast cancer by simultaneously inhibiting PI3K signaling and degrading ER. This regimen has shown feasibility, tolerability, and preliminary clinical activity in early-phase trials for heavily pretreated patients[1][2][6].