Kisqali

HR+/HER2− Advanced or Metastatic Breast Cancer: In combination with an aromatase inhibitor as initial endocrine-based therapy in pre/perimenopausal or postmenopausal women and men.
HR+/HER2− Advanced or Metastatic Breast Cancer: In combination with fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy in postmenopausal women and men.
HR+/HER2− Early Breast Cancer (adjuvant): In combination with an aromatase inhibitor in adult patients with high risk of recurrence (node-positive, ≥4 positive nodes or 1–3 nodes with Grade 3 or tumor ≥5 cm).

Advanced/metastatic: 600 mg orally once daily for 21 consecutive days followed by 7 days off (28-day cycle)
Adjuvant early breast cancer: 400 mg orally once daily for 21 consecutive days followed by 7 days off (28-day cycle) for 3 years
Administration: With or without food. Swallow tablets whole.
Dose reductions (advanced): First: 400 mg; Second: 200 mg. Discontinue if unable to tolerate 200 mg.
Dose reductions (adjuvant): First: 200 mg. Discontinue if unable to tolerate 200 mg.

Tablets (film-coated): 200 mg, 400 mg, 600 mg

None listed in the prescribing information.

• Neutropenia: Monitor CBCs prior to initiation, every 2 weeks for first 2 cycles, at the beginning of each subsequent cycle, and as clinically indicated.
• Hepatobiliary Toxicity: ALT/AST elevations reported. Monitor LFTs before initiation, every 2 weeks for first 2 cycles, at beginning of subsequent 4 cycles, then as clinically indicated.
• QT Interval Prolongation: Monitor ECGs prior to initiation, at approximately Day 14 of Cycle 1, at beginning of Cycle 2, and as clinically indicated. Avoid in patients with long QT syndrome.
• ILD/Pneumonitis: Reported including fatal cases. Monitor and permanently discontinue for severe ILD/pneumonitis.
• Embryo-Fetal Toxicity: Can cause fetal harm. Verify pregnancy status before initiating.

Neutropenia (74%), Nausea (52%), Infections (50%), Fatigue (37%), Diarrhea (35%), Leukopenia (33%), Vomiting (29%), Alopecia (27%), Headache (22%), Constipation (21%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Strong CYP3A Inhibitors: Avoid concurrent use. If unavoidable, reduce Kisqali dose (600→400, 400→200 mg).
Strong CYP3A Inducers: Avoid concurrent use.
CYP3A Substrates: Ribociclib is a strong CYP3A inhibitor. Concomitant use with sensitive CYP3A substrates with narrow therapeutic index should be avoided.
QT Prolonging Drugs: Avoid concomitant use with drugs known to prolong QT interval.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Ribociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). These kinases are activated upon binding to D-cyclins and play a critical role in signaling pathways leading to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb). Ribociclib inhibits pRb phosphorylation, preventing G1/S cell cycle progression and reducing proliferation.

Tmax: 1–5 hours. Bioavailability: ~32%. Vd: 1090 L. Protein binding: 70%. Metabolized primarily by CYP3A4. Half-life: 32 hours. Steady state by Day 8. Elimination: feces 69%, urine 23%.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• MONALEESA-2 — Ribociclib + letrozole vs. placebo + letrozole as first-line in HR+/HER2− advanced breast cancer (postmenopausal). Phase III, n=668.
  🔬 NCT01958021 ↗ 📄 Primary Publication ↗
• MONALEESA-3 — Ribociclib + fulvestrant vs. placebo + fulvestrant in HR+/HER2− advanced breast cancer (postmenopausal). Phase III, n=726.
  🔬 NCT02422615 ↗ 📄 Primary Publication ↗
• MONALEESA-7 — Ribociclib + endocrine therapy vs. placebo + endocrine therapy in pre/perimenopausal HR+/HER2− advanced breast cancer. Phase III, n=672.
  🔬 NCT02278120 ↗ 📄 Primary Publication ↗
• NATALEE — Adjuvant ribociclib + NSAI vs. NSAI alone in HR+/HER2− early breast cancer. Phase III, n=5101.
  🔬 NCT03701334 ↗ 📄 Primary Publication ↗

Kisqali has FDA-approved indications across the following cancer types covered on PipelineEvidence: