inavolisib + ribociclib + letrozole

**Inavolisib + ribociclib + letrozole** is a combination therapy under clinical investigation for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer. This regimen combines three targeted agents: - **Inavolisib** is a potent, selective, oral inhibitor of phosphoinositide 3-kinase alpha (PI3Kα), specifically promoting the degradation of mutated p110α (encoded by PIK3CA), which is implicated in oncogenesis in PIK3CA-mutated cancers. - **Ribociclib** is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, interfering with cell cycle progression and proliferation of cancer cells. - **Letrozole** is a non-steroidal aromatase inhibitor that suppresses estrogen synthesis. The combination targets the PI3K pathway, cell cycle progression, and estrogen signaling, addressing resistance mechanisms in HR+ breast cancer. The regimen is being developed and led in trials primarily by Genentech/Roche. Primary indication: HR+, HER2−, PIK3CA-mutated locally advanced or metastatic breast cancer, and is being tested in early and advanced disease[1][2][4].