ribociclib

Ribociclib is an oral anticancer medication that selectively inhibits cyclin-dependent kinases 4 and 6 (CDK4/6). It is approved for adults with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer. It is marketed as Kisqali and was developed by Novartis.

Mechanism of action: CDK4/6 inhibitors block phosphorylation of the retinoblastoma protein, preventing progression from G1 to S phase and slowing cancer cell proliferation.

Indications and use: In the United States, ribociclib is approved in combination with letrozole as initial endocrine therapy for postmenopausal women with HR+, HER2− advanced breast cancer, and in combination with fulvestrant for patients whose disease progressed after prior endocrine therapy. It has also been studied in premenopausal settings with ovarian suppression. The evidence base includes pivotal trials demonstrating improvements in progression-free survival and, in some settings, overall survival.

Administration and dosing: The typical dose is 600 mg orally once daily on days 1–21 of a 28-day cycle, in combination with letrozole 2.5 mg daily. When used with fulvestrant, ribociclib is given at 600 mg daily on days 1–21 of a 28-day cycle, with fulvestrant dosing per standard schedule. Dose adjustments are allowed for adverse events or drug interactions.

Safety and monitoring: Common adverse events include neutropenia, leukopenia, nausea, fatigue, diarrhea, vomiting, alopecia, and elevated liver enzymes. QT interval prolongation is a potential risk. Ribociclib can cause hepatotoxicity and myelosuppression; patients require regular blood tests and liver function monitoring, and ECG monitoring as indicated. It is contraindicated in pregnancy; use with contraception is advised. Being metabolized by CYP3A4, strong inhibitors or inducers can alter exposure, necessitating dose modifications.