alpelisib + everolimus + exemestane

This is a combination therapy consisting of three small molecule drugs: alpelisib, everolimus, and exemestane. Alpelisib is a selective inhibitor of the phosphatidylinositol 3-kinase catalytic subunit p110α (PI3Kα), targeting the PI3K/AKT/mTOR pathway. Everolimus is an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), also acting on the PI3K/AKT/mTOR signaling cascade. Exemestane is a steroidal aromatase inhibitor that suppresses estrogen synthesis by irreversibly binding to and inactivating aromatase, thereby reducing estrogen-driven tumor growth in hormone receptor-positive cancers. The rationale for combining these agents lies in their complementary mechanisms: dual blockade of PI3Kα and mTORC1 can overcome resistance mechanisms within the pathway, while concurrent estrogen suppression with exemestane targets hormone-dependent tumor proliferation. This combination has been studied primarily in advanced solid tumors—including postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer—especially after progression on prior endocrine therapies or mTOR inhibitors[1]. The safety profile is manageable and reversible; pharmacokinetics are not significantly altered when used together[1].

Brand names

Piqray (alpelisib)Afinitor (everolimus)Aromasin (exemestane)