Palbociclib is an oral selective inhibitor of CDK4 and CDK6. Its pharmacologic effect interferes with cell-cycle progression and forms the basis for its use in selected breast cancer treatment settings.
Pharmacodynamics
CDK4 and CDK6 are involved in regulating the transition from the G1 phase toward S phase of the cell cycle. Palbociclib inhibits these kinases, reducing phosphorylation of retinoblastoma protein and limiting cell-cycle progression.
Pharmacokinetics
For the current tablet formulation, maximum plasma concentrations are generally observed approximately 4 to 12 hours after oral administration. The mean absolute bioavailability after a 125 mg oral dose is approximately 46%.
For capsules, current labeling describes a mean absolute bioavailability of approximately 46% after 125 mg and steady state within approximately 8 days of repeated once-daily administration.
Protein binding
Palbociclib is approximately 85% bound to human plasma proteins in vitro.
Metabolism
Palbociclib undergoes extensive hepatic metabolism. CYP3A and SULT2A1 contribute substantially to its metabolism.
Elimination
The mean plasma elimination half-life in patients with advanced breast cancer is approximately 29 ± 5 hours. Most of the administered radioactive dose was recovered as metabolites, with feces representing the major route of recovery in the radiolabeled study.
QT pharmacodynamics
In an evaluation involving 77 patients with breast cancer, palbociclib at 125 mg once daily for 21 days followed by 7 days off did not have a large effect on QTc.
PALOMA-2
PALOMA-2 evaluated palbociclib plus letrozole in postmenopausal women with previously untreated ER-positive/HER2-negative advanced breast cancer.
The initial analysis reported median progression-free survival of 24.8 months with palbociclib plus letrozole compared with 14.5 months with placebo plus letrozole.
PALOMA-3
PALOMA-3 evaluated palbociclib plus fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer whose disease had progressed following endocrine therapy. The study contributed to the expansion of the FDA indication for palbociclib with fulvestrant.
PATINA
PATINA evaluated palbociclib with anti-HER2 therapy and endocrine therapy as maintenance treatment in HR-positive/HER2-positive metastatic breast cancer after induction treatment. The FDA approved this treatment setting in June 2026.
Clinical interpretation
Clinical-trial results describe populations studied under defined protocols. They do not establish that every patient with breast cancer will respond to palbociclib.