Information about Ribociclib
Ribociclib is a unique cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer.
Liver safety of Ribociclib
Ribociclib is associated with a moderate rate of serum aminotransferase elevations during therapy, and to clinically apparent liver injury in a proportion of these.
Mechanism of action of Ribociclib
Ribociclib (rye" boe sye' klib) is an orally available, small molecule inhibitor of cyclin-dependent kinases 4 and 6 that is used in combination with aromatase inhibitors in the therapy of postmenopausal women with metastatic breast cancer that is positive for the estrogen hormone receptor (ER+), but negative for human epidermal growth factor receptor 2 (HER2-). The cyclin kinases 4 and 6 regulate the cellular transition from the G1 to the S phase of the cell cycle acting through the retinoblastoma protein (Rb) pathway. Inhibition of this transition blocks the progression of the cell cycle and results in growth arrest in rapidly dividing cells. Components of this pathway are often mutated or overexpressed in cancer cells. In several clinical trials, the addition of ribociclib to letrozole (aromatase inhibitor) therapy of advanced or metastatic breast cancer (ER+, HER2-) in postmenopausal women was associated with a prolongation of disease-free but not overall survival.
FDA approval information for Ribociclib
Ribociclib received accelerated approval for use in the United States in 2017. Ribociclib is under investigation as therapy of several solid tumors and lymphomas, but the initial indications were limited to advanced or metastatic ER+, HER2- breast cancer in postmenopausal women given in combination with an aromatase inhibitor.
Dosage and administration for Ribociclib
Ribociclib is available in tablets of 200 mg under the brand name Kisqali, and the initial recommended dose is 600 mg once daily in 21 day cycles every 28 days indefinitely or until there is disease progression.
Side effects of Ribociclib
Common side effects include neutropenia, fatigue, nausea, diarrhea, anorexia, thrombocytopenia, headache and back pain. Less common, but potentially severe adverse reactions include prolongation of the QTc interval, severe neutropenia, fever and infections, and embryo-fetal toxicity.