Ribociclib is a kinase inhibitor indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with:

• an aromatase inhibitor as initial endocrine-based therapy; or
• fulvestrant as initial endocrine-based therapy or after disease progression on prior endocrine therapy in postmenopausal women or in men.

Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases become active after binding with D-cyclins and play an essential role in signaling pathways that control cell cycle progression and cellular proliferation. The cyclin D–CDK4/6 complex regulates the cell cycle through phosphorylation of the retinoblastoma protein (pRb). In vitro studies show that ribociclib reduces pRb phosphorylation, resulting in G1 phase cell cycle arrest and decreased proliferation of breast cancer cells. In vivo studies using rat xenograft models demonstrated reduced tumor volume after ribociclib treatment, which correlated with inhibition of pRb phosphorylation. In patient-derived estrogen receptor–positive breast cancer xenograft models, ribociclib combined with antiestrogens (such as letrozole) produced greater tumor growth inhibition compared to either drug alone. Additionally, the combination of ribociclib with fulvestrant also showed significant tumor growth inhibition in estrogen receptor–positive breast cancer models.

Ribociclib tablets are taken orally with or without food in combination with an aromatase inhibitor or fulvestrant.

• Recommended starting dose: 600 mg orally (three 200 mg tablets) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment.
• Dose interruption, reduction, and/or discontinuation may be required based on individual safety and tolerability.

CYP3A4 Inhibitors: Avoid concomitant use of Ribociclib with strong CYP3A inhibitors. If unavoidable, reduce the Ribociclib dose.

CYP3A4 Inducers: Avoid concomitant use of Ribociclib with strong CYP3A inducers.

CYP3A Substrates: The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced when used with Ribociclib.

QT-Prolonging Drugs: Avoid concomitant use with medicines known to prolong the QT interval, such as antiarrhythmic drugs.

Most common adverse reactions (≥20%), including laboratory abnormalities, include decreased leukocytes, neutrophils, hemoglobin, and lymphocytes; increased AST, ALT, and gamma-glutamyl transferase; infections; nausea; increased creatinine; fatigue; decreased platelets; diarrhea; vomiting; headache; constipation; alopecia; cough; rash; back pain; and decreased serum glucose.

Based on animal studies and mechanism of action, Ribociclib may cause fetal harm when used in pregnancy. It is unknown whether Ribociclib is excreted in human milk. No data are available regarding its effects on the breastfed infant or milk production.

Interstitial Lung Disease (ILD)/Pneumonitis: Monitor patients for respiratory symptoms. Interrupt treatment if ILD/pneumonitis is suspected. Permanently discontinue in severe or recurrent cases.

Severe Cutaneous Adverse Reactions (SCARs): Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and DRESS may occur. Permanently discontinue Ribociclib if SCARs develop.

QT Prolongation: Perform ECG and electrolyte monitoring before and during treatment. Avoid use with QT-prolonging drugs and strong CYP3A inhibitors.

Tamoxifen Use: Concomitant use with tamoxifen is not recommended due to increased QT prolongation risk.

Hepatobiliary Toxicity: Monitor liver function tests before and during treatment.

Neutropenia: Perform regular complete blood counts before and during therapy.

Embryo-Fetal Toxicity: May cause fetal harm. Advise effective contraception during treatment.

Targeted Cancer Therapy

Store below 30°C, protected from light and moisture. Keep out of reach of children.