Ribociclib — Drug Monograph

Brand names: Kisqali

Drug class: CDK4/6 Inhibitor

Mechanism of Action

Selective CDK4/6 inhibitor structurally distinct from palbociclib and abemaciclib. Ribociclib inhibits CDK4/6-cyclin D complexes, preventing Rb protein phosphorylation and blocking G1-to-S phase cell cycle progression in hormone receptor-positive cancer cells where CDK4/6 activity is amplified. The CDK4/6 axis is the primary driver of cell cycle entry in ER-positive tumors, explaining the dramatic activity of CDK4/6 inhibitors in HR+ breast cancer. Like palbociclib, ribociclib is administered on a 3-weeks-on/1-week-off schedule. Unlike palbociclib, ribociclib carries a risk of QTc…

FDA Indications

• HR+/HER2-negative breast cancer — advanced/metastatic, first-line (with aromatase inhibitor — MONALEESA-2 [postmenopausal], MONALEESA-7 [pre/perimenopausal with goserelin])
• HR+/HER2-negative breast cancer — advanced/metastatic, first-line or second-line (with fulvestrant — MONALEESA-3)
• HR+/HER2-negative breast cancer — early stage, high risk (node-positive), adjuvant (with aromatase inhibitor — NATALEE trial: 3 years of ribociclib)

Common Side Effects

• Neutropenia (most common hematologic toxicity; dose-limiting)
• Nausea
• Fatigue
• Diarrhea (less than abemaciclib)
• Alopecia
• Vomiting
• Constipation
• Leukopenia
• Headache
• Back pain

Clinical Pearl

Ribociclib is the only CDK4/6 inhibitor with demonstrated OS benefit in both premenopausal (MONALEESA-7: OS HR 0.71) and postmenopausal (MONALEESA-3: OS HR 0.73) women with HR+/HER2- metastatic breast cancer. QTc monitoring is mandatory — baseline ECG, Day 14 (when QTc peak occurs), and Cycle 2 Day 1. Concomitant ondansetron (a QTc-prolonging antiemetic) and ribociclib should be avoided. Hepatotoxicity requires more intensive LFT monitoring than with palbociclib.

Related Therapies & Mechanisms

• Abemaciclib (Verzenio) — CDK4/6 Inhibitor · Breast
• Palbociclib (Ibrance) — CDK4/6 Inhibitor · Breast
• Trilaciclib (Cosela) — CDK4/6 Inhibitor
• 5-Fluorouracil (5-FU) (Adrucil) — Breast