Ribociclib

KISQALI is a kinase inhibitor indicated: in combination with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence. for the treatment of adults with HR-positive, 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 following disease progression on endocrine therapy.

Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to D-cyclins and are downstream of signaling 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 and reduced proliferation in breast cancer-derived models. In vivo, treatment with single agent ribociclib in a rat xenograft model with human tumor cells led to decreased tumor volumes, which correlated with inhibition of pRb phosphorylation.

KISQALI tablets are taken orally with or without food in combination with an aromatase inhibitor or fulvestrant. Early Breast Cancer Recommended starting dose: 400 mg orally (two 200 mg tablets) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment. Advanced or Metastatic Breast Cancer 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.

None. None.

Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life threatening, or fatal ILD/pneumonitis can occur with KISQALI treatment. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Interrupt and evaluate patients with new or worsening respiratory symptoms suspected to be due to ILD/pneumonitis. Permanently discontinue KISQALI in patients with recurrent symptomatic or severe ILD/pneumonitis. Severe Cutaneous Adverse Reactions (SCARs): SCARs including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-reaction with eosinophilia and systemic symptoms (DRESS) can occur with KISQALI treatment. Permanently discontinue KISQALI in patients with SCARs or other life-threatening cutaneous reactions. QT Interval Prolongation: KISQALI has been shown to prolong the QT interval in a concentration-dependent manner.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Interstitial Lung Disease/Pneumonitis Severe Cutaneous Adverse Reactions QT Interval Prolongation Hepatotoxicity Neutropenia In patients with early breast cancer, the most common (incidence ≥ 20%) adverse reactions, including laboratory abnormalities, are lymphocytes decreased, leukocytes decreased, neutrophils decreased, hemoglobin decreased, alanine aminotransferase increased, aspartate aminotransferase increased, infections, creatinine increased, platelets decreased, headache, nausea, and fatigue.

CYP3A Inhibitors: Avoid concomitant use of KISQALI with strong CYP3A inhibitors. If strong inhibitors cannot be avoided, reduce KISQALI dose. CYP3A4 Inducers: Avoid concomitant use of KISQALI with strong CYP3A inducers. CYP3A Substrates: The dose of CYP3A substrates may need to be reduced when given concurrently with KISQALI. Drugs Known to Prolong QT Interval: Avoid concomitant use of drugs known to prolong QT interval, such as anti-arrhythmic medicines.

Store at room temperature at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Store in the original blister package in order to protect from moisture.