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**Ribociclib + letrozole** is an oral endocrine-targeted anticancer combination for hormone receptor-positive, HER2-negative breast cancer. Ribociclib is a selective cyclin-dependent kinase 4 and 6 inhibitor that suppresses retinoblastoma-pathway phosphorylation and inhibits G1-to-S cell-cycle progression, while letrozole is a nonsteroidal aromatase inhibitor that reduces estrogen synthesis and estrogen-receptor signaling. The combination is used as endocrine-based therapy in locally advanced or metastatic disease and is also available in the United States as the co-packaged product **Kisqali Femara Co-Pack** for eligible patients with high-risk stage II or III early breast cancer. ([accessdata.fda.gov](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209935s030lbl.pdf))
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