Last reviewed 2026-04-20 · How we verify

Palbociclib (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 in combination with endocrine therapy or with inavolisib and fulvestrant for PIK3CA-mutated disease. The drug has moderate bioavailability (46%) with food-dependent absorption and is primarily metabolized by CYP3A, requiring dose adjustments with strong CYP3A inhibitors. Major drug interactions include strong CYP3A inhibitors and inducers that significantly alter palbociclib exposure. Clinical use requires careful monitoring of concomitant medications and consideration of hepatic function due to increased unbound drug fraction with worsening liver disease.

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. The combination also led to increased cell senescence that 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

• Treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy
• Treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with fulvestrant in patients with disease progression following endocrine therapy
• Treatment of adult patients with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy, in combination with inavolisib and fulvestrant

Common side effects

• Neutropenia
• Neutrophil Count Decreased
• Arthralgia
• Fatigue
• Stomatitis
• Nausea
• Hot Flush
• Diarrhoea
• Alopecia
• Constipation
• Headache
• Vomiting

Drug interactions

• Strong CYP3A inhibitors (clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole)
• Grapefruit or 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

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Palbociclib CI brief — competitive landscape report
• Palbociclib updates RSS · CI watch RSS
• Pfizer Inc. portfolio CI