Ibrance

HR+/HER2− Advanced or Metastatic Breast Cancer: In combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women or men.
HR+/HER2− Advanced or Metastatic Breast Cancer: In combination with fulvestrant in patients with disease progression following endocrine therapy.
PIK3CA-mutated Breast Cancer: In combination with inavolisib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR+/HER2− locally advanced or metastatic breast cancer following recurrence on or after adjuvant endocrine therapy.

Standard dose: 125 mg orally once daily for 21 consecutive days followed by 7 days off treatment (28-day cycle)
Administration: Take with food
Dose reductions: First reduction: 100 mg/day; Second reduction: 75 mg/day. Discontinue if unable to tolerate 75 mg.
Strong CYP3A inhibitor: Reduce dose to 75 mg/day. If inhibitor discontinued, increase after 3–5 half-lives.
Severe hepatic impairment (Child-Pugh C): 75 mg/day

Capsules: 75 mg, 100 mg, 125 mg. Tablets: 75 mg, 100 mg, 125 mg.

None listed in the prescribing information.

• Neutropenia: Most frequently reported adverse reaction (up to 83%). Monitor CBCs prior to starting, at the beginning of each cycle, on Day 15 of the first 2 cycles, and as clinically indicated. Dose interruption, reduction, or delay recommended for Grade 3–4 neutropenia.
• ILD/Pneumonitis: Reported in post-marketing with fatalities. Monitor for pulmonary symptoms. Permanently discontinue for severe ILD/pneumonitis.
• Embryo-Fetal Toxicity: Can cause fetal harm. Verify pregnancy status before initiating. Advise effective contraception.

Neutropenia (80%), Infections (60%), Leukopenia (39%), Fatigue (37%), Nausea (35%), Alopecia (33%), Stomatitis (30%), Diarrhea (26%), Anemia (24%), Thrombocytopenia (16%)

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

Strong CYP3A Inhibitors: Avoid concurrent use. If unavoidable, reduce Ibrance dose to 75 mg/day.
Strong CYP3A Inducers: Avoid concurrent use (e.g., rifampin, phenytoin, carbamazepine, St. John's wort).
CYP3A Substrates: Palbociclib is a time-dependent CYP3A inhibitor. Dose of sensitive CYP3A substrates with narrow therapeutic index may need reduction.

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.

Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). CDK4/6 are downstream of multiple signaling pathways involved in cell proliferation. Palbociclib reduces cellular proliferation of ER-positive breast cancer cell lines by blocking progression of the cell from G1 into the S phase of the cell cycle. Combining palbociclib with anti-estrogen therapy leads to increased growth inhibition compared to either agent alone.

Tmax: 4–12 hours. Bioavailability: 46% (125 mg dose). Steady state within 8 days; accumulation ratio 2.4. Vd: 2583 L. Protein binding: ~85%. Metabolized primarily by CYP3A and SULT2A1. Half-life: 29 hours (±5). Elimination: feces 74%, urine 18%.

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

• PALOMA-2 — Palbociclib + letrozole vs. placebo + letrozole in first-line ER+/HER2− advanced breast cancer. Phase III, n=666.
  🔬 NCT01740427 ↗ 📄 Primary Publication ↗
• PALOMA-3 — Palbociclib + fulvestrant vs. placebo + fulvestrant in HR+/HER2− advanced breast cancer after prior endocrine therapy. Phase III, n=521.
  🔬 NCT01942135 ↗ 📄 Primary Publication ↗

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