Last reviewed 2026-04-20 · How we verify

Ibrance (Palbociclib)

Palbociclib inhibits CDK4/6 to block G1/S cell cycle progression in ER-positive breast cancer.

Palbociclib is a CDK4/6 inhibitor indicated for HR-positive, HER2-negative advanced or metastatic breast cancer combined with endocrine therapy or inavolisib/fulvestrant. It demonstrates strong efficacy by blocking G1/S cell cycle progression and enhancing growth arrest when combined with antiestrogens. Major risks include increased exposure with CYP3A inhibitors (requiring dose reduction) and decreased exposure with CYP3A inducers. The drug represents a significant therapeutic advance in hormone receptor-positive breast cancer management with established clinical benefit.

At a glance

Mechanism of action

Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6, which are downstream of signaling pathways leading to cellular proliferation. In vitro, palbociclib reduced cellular proliferation of estrogen receptor (ER)-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle. When combined with antiestrogens, palbociclib treatment leads to decreased retinoblastoma (Rb) protein phosphorylation resulting in reduced E2F expression and signaling, with increased growth arrest compared to treatment with each drug alone. In vitro treatment also led to increased cell senescence compared to each drug alone, which was sustained for up to 6 days following palbociclib removal. In vivo studies using a patient-derived ER-positive breast cancer xenograft model demonstrated that the combination of palbociclib and letrozole increased the inhibition of Rb phosphorylation, downstream signaling, and tumor growth compared to each drug alone.

Approved indications

• Hormone receptor positive malignant neoplasm of breast
• Human epidermal growth factor 2 negative carcinoma of breast

Common side effects

• Neutrophil count decreased
• Fatigue
• Diarrhea
• Platelet count decreased
• Nausea
• Neutropenia
• Headache
• Aspartate aminotransferase increased
• White blood cell decreased
• White blood cell count decreased
• Alanine aminotransferase increased
• Arthralgia

Drug interactions

• Strong CYP3A inhibitors (clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole)
• Grapefruit and grapefruit juice
• Strong CYP3A inducers (phenytoin, rifampin, carbamazepine, enzalutamide, St John's Wort)
• Sensitive CYP3A4 substrates with narrow therapeutic indices (e.g., midazolam)

Patents

Primary sources

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