Last reviewed 2026-04-20 · How we verify

Kisqali (ribociclib)

Ribociclib inhibits CDK4/6 kinases to arrest G1 cell cycle phase; letrozole inhibits aromatase to reduce estrogen biosynthesis.

KISQALI FEMARA CO-PACK combines ribociclib (CDK4/6 inhibitor) and letrozole (aromatase inhibitor) for HR-positive, HER2-negative breast cancer. It is indicated for adjuvant treatment of early breast cancer at high risk of recurrence and as initial endocrine-based therapy for advanced or metastatic disease. Strong CYP3A4 inhibitors increase ribociclib exposure requiring dose reduction; strong inducers should be avoided. The combination demonstrates superior tumor growth inhibition compared to single agents in preclinical models.

At a glance

Mechanism of action

Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6, which are activated upon binding to D-cyclins and regulate 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 cell proliferation in breast cancer-derived lines. In vivo, treatment with single agent ribociclib in a rat xenograft model led to decreased tumor volumes, correlating with inhibition of pRb phosphorylation. Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system by competitively binding to the heme of the cytochrome P450 subunit, resulting in reduction of estrogen biosynthesis in all tissues. In postmenopausal women, estrogens are mainly derived from the aromatase enzyme, which converts adrenal androgens to estrone and estradiol. Suppression of estrogen biosynthesis in peripheral tissues and cancer tissue is achieved by specifically inhibiting the aromatase enzyme. In patient-derived estrogen receptor positive breast cancer xenograft models, combination of ribociclib and antiestrogen therapies resulted in increased tumor growth inhibition compared to each drug alone.

Approved indications

• Hormone receptor positive malignant neoplasm of breast

Common side effects

• Neutropenia
• Nausea
• Fatigue
• Alanine aminotransferase increased
• Aspartate aminotransferase increased
• Leukopenia
• Arthralgia
• Headache
• Constipation
• Neutrophil Count Decreased
• Vomiting
• Anaemia

Drug interactions

• Strong CYP3A4 inhibitors
• Strong CYP3A4 inducers
• CYP3A substrates with narrow therapeutic indices
• Drugs known to prolong QT interval (e.g., anti-arrhythmic medicines)

Key clinical trials

• Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial (PHASE3)
• Study of ECI830 Single Agent or in Combination in Patients With Advanced HR+/HER2- Breast Cancer and Other Advanced Solid Tumors (PHASE1,PHASE2)
• BGB-43395 Plus Letrozole Versus CDK4/6i Plus Letrozole for Patients With Advanced or Metastatic HR+/HER2- Breast Cancer Who Have Not Received Prior Treatment for Advanced or Metastatic Disease (PHASE3)
• Validation of Capillary Microsampling for Therapeutic Drug Monitoring of CDK4/6 Inhibitors in Breast Cancer Patients (TDHOME) (NA)
• Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors (PHASE1)
• Ribociclib And Endocrine Treatment of Physician's Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer (PHASE2)
• Clinical and Pharmacoeconomic Assessment of CDK4/6 Inhibitors for Treatment of Breast Cancer in Egypt (PHASE4)
• A Study of Tersolisib (LY4064809/STX-478) With Other Anti-Cancer Treatments in Participants With Advanced Breast Cancer With a Genetic Change (PIK3CA) (PHASE3)

Patents

Primary sources

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