Ribociclib is a cyclin-dependent kinase (CDK) 4 and 6 inhibitor used in the treatment of hormone receptor-positive, HER2-negative breast cancer. It is given together with an aromatase inhibitor for the adjuvant treatment of adults with stage II and III early breast cancer at high risk of recurrence. In advanced or metastatic disease, it is used together with an aromatase inhibitor or with fulvestrant, either as initial endocrine-based therapy or after earlier endocrine therapy.
Early Breast Cancer in Combination with An Aromatase Inhibitor for Adjuvant Treatment of Patients with Hormone Receptor-positive, Her2-negative Early Breast Cancer At High Risk of Recurrence
200mg
Treats hormone receptor-positive, HER2-negative breast cancer by inhibiting cyclin-dependent kinases 4 and 6, thereby halting cancer cell division and slowing tumour growth.
Early Breast Cancer in Combination with An Aromatase Inhibitor for Adjuvant Treatment of Patients with Hormone Receptor-positive, Her2-negative Early Breast Cancer At High Risk of Recurrence
200mg
Treats hormone receptor-positive HER2-negative breast cancer by inhibiting cyclin-dependent kinases 4 and 6 to halt cancer cell division and slow tumour growth.
Ribociclib is a selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6, resulting in 50% inhibition (IC50) values of 0.01 (4.3 ng/ml) and 0.039 μM (16.9 ng/ml) in biochemical assays, respectively. These kinases are activated upon binding to D-cyclins and play a crucial role in signalling pathways which lead to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb). In vitro, ribociclib decreased pRb phosphorylation, resulting in arrest in the G1 phase of the cell cycle, reduced proliferation and a senescent phenotype in breast cancer derived models. In a rat xenograft model using human tumour cells, single-agent ribociclib led to decreased tumour volumes that correlated with inhibition of pRb phosphorylation.
Ribociclib is contraindicated in patients with hypersensitivity to the active substance or to peanut, soya, or any of its excipients.
Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. It should be avoided in patients at significant risk of developing Torsades de Pointes (TdP), including those with uncontrolled or significant cardiac disease, a recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, uncontrolled hypertension, high degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism.
Drug-induced liver injury and increases in transaminases have occurred in patients treated with ribociclib. In the early breast cancer trial, drug-induced liver injury was reported in 9 patients (0.4%), of which 5 were graded 3 or higher, and 8 of the 9 had resolved by the data cutoff. There were also 8 (0.3%) clinically confirmed Hy’s Law cases, 6 of which had resolved within 303 days and 2 of which were improving, all after ribociclib was stopped. Liver function tests should be carried out before starting treatment, and liver function should be monitored after treatment begins.
Ribociclib causes concentration-dependent neutropenia. In the early breast cancer trial, 94% of patients taking ribociclib with an aromatase inhibitor had a laboratory-confirmed fall in neutrophil counts, including 45% graded 3 or 4; 63% had a reported adverse reaction of neutropenia, and 0.3% had febrile neutropenia. The median time to grade 2 or higher neutropenia was 18 days. A complete blood count should be carried out in all patients before starting ribociclib.
Ribociclib can also cause harm to a developing baby. The label states that, based on animal studies and its mechanism of action, it can cause fetal harm when given to a pregnant woman, and asks that pregnant women be advised of the potential risk to a fetus.
