Palbociclib

Palbociclib is an oral, selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) used in the treatment of certain breast cancers. By inhibiting CDK4/6, it prevents phosphorylation of the retinoblastoma (RB) protein, causing G1 cell cycle arrest and reduced tumor cell proliferation. It is one of several CDK4/6 inhibitors approved for hormone receptor–positive, HER2-negative breast cancer.

Indications and use: Palbociclib is approved for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with endocrine therapy. It is typically used with letrozole as initial endocrine therapy and with fulvestrant in patients whose disease progressed after aromatase inhibitor therapy. Regulatory approvals vary by country, but the agent is commonly indicated in combination with an aromatase inhibitor or with fulvestrant in appropriate settings.

Administration and dosing: The standard dosing is 125 mg once daily on days 1–21 of a 28-day cycle. When combined with letrozole, letrozole is given continuously at 2.5 mg daily. When combined with fulvestrant, fulvestrant is given per its standard dosing schedule. Dose adjustments are recommended for hematologic toxicities and other adverse events. Palbociclib is a substrate of CYP3A and may interact with strong CYP3A inhibitors or inducers, requiring dose modification or avoidance of interacting drugs.

Adverse effects and monitoring: Common adverse effects include neutropenia, leukopenia, fatigue, nausea, anemia, and infections. Regular complete blood counts are required before and during treatment. Palbociclib is used with caution in pregnancy and in patients with liver impairment.

Clinical context: Palbociclib is one of several CDK4/6 inhibitors shown to improve progression-free survival when added to endocrine therapy in HR-positive, HER2-negative breast cancer. Overall survival benefits vary by trial and line of therapy.