General Information

Kisqali (ribociclib) is a kinase inhibitor.

Kisqali is specifically indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

Mechanism of Action

Kisqali (ribociclib) is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to Dcyclins and play a crucial role in 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 leading to arrest in the G1 phase of the cell cycle and reduced cell proliferation in breast cancer cell lines. 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. In studies using patient-derived estrogen receptor positive breast cancer xenograft models, combination of ribociclib and antiestrogen (e.g., letrozole) resulted in increased tumor growth inhibition compared to each drug alone.

Side Effects

Adverse effects associated with the use of Kisqali may include, but are not limited to, the following:

Neutropenia

Nausea

Fatigue

Diarrhea

Leukopenia

Alopecia

Vomiting

Constipation

Headache

Back pain

Dosing/Administration

Kisqali is supplied as a tablet for oral administration. The recommended dose of Kisqali is 600 mg (three 200 mg film-coated tablets) taken orally, once daily, for 21 consecutive days followed by seven days off treatment resulting in a complete cycle of 28 days. Kisqali can be taken with or without food. Co-administer Kisqali with letrozole 2.5 mg taken once daily throughout the 28-day cycle. Refer to the full prescribing information of letrozole. For dosing and administration with other aromatase inhibitors refer to the applicable full prescribing information. Patients should take their dose of Kisqali and letrozole at approximately the same time each day, preferably in the morning. If the patient vomits after taking the dose or misses a dose, no additional dose should be taken that day. The next prescribed dose should be taken at the usual time. Kisqali tablets should be swallowed whole; tablets should not be chewed, crushed or split prior to swallowing.

Clinical Trial Results

FDA approval of Kisqali was based on a randomized, double-blind, placebo-controlled, international clinical trial (MONALEESA-2), in post-menopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer who received no prior therapy for advanced disease. A total of 668 women were randomized to receive either ribociclib plus letrozole (n=334) or placebo plus letrozole (n=334). Ribociclib 600 mg or placebo was administered orally once daily for 21 consecutive days, followed by seven days off, with letrozole 2.5 mg administered orally once daily for 28 days. Treatment continued until disease progression or unacceptable toxicity. A pre-planned interim efficacy analysis demonstrated an improvement in PFS (investigator-assessed) (p<0.0001). The estimated median PFS had not been reached in the ribociclib-containing arm and was 14.7 months in the placebo-containing arm. Objective response rate (ORR) in patients with measurable disease was 52.7 percent in the ribociclib plus letrozole arm and 37.1 percent in the placebo plus letrozole arm. Overall survival data were immature.