Palbociclib is a protein kinase inhibitor which selectively and reversibly inhibits cyclin-dependent kinases (CDK) 4 and 6. Cyclin-D1 and CDK4/6 are downstream of multiple signalling pathways which lead to cellular proliferation.
Palbociclib should be used in combination with an aromatase inhibitor, or with fulvestrant in women who have received prior endocrine therapy. In women who are pre- or perimenopausal the endocrine therapy should be combined with an LHRH agonist.
The efficacy of palbociclib in combination with letrozole or fulvestrant was assessed in two randomised placebo-controlled trials involving women with hormone receptor positive HER2-negative locally advanced or metastatic breast cancer. In both studies the primary endpoint was investigator-assessed progression-free survival evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST).
In the PALOMA-2 study, 666 women were randomised to receive letrozole plus palbociclib (n=444) or placebo (n=222). Progression-free survival was improved in the palbociclib group compared with the placebo group (median of 24.8 months vs 14.5 months; hazard ratio for disease progression or death, 0.58; 95% CI 0.46–0.72, p<0.001).
Similarly, in the PALOMA-3 study, women receiving fulvestrant plus palbociclib (n=347) had improved progression-free survival compared with those receiving palbociclib plus placebo (n=174, median 9.5 months vs 4.6 months; hazard ratio 0.46, 95% CI 0.36–0.59, p<0.0001).
The most commonly reported adverse effects in the two trials were neutropenia, infections, leucopenia, fatigue, nausea, stomatitis, anaemia, alopecia and diarrhoea.