Difference Between CDK Inhibitors

What is the difference between the CDK inhibitors? —Name withheld on request

At the time of this writing, there are 2 cyclin-dependent kinase (CDK) inhibitors approved for use in the United States: palbociclib (Ibrance) and ribociclib (Kisqali). A third agent, abemaciclib, is currently in development but is not yet approved for use by the Food and Drug Administration (FDA).

These CDK inhibitors work by inhibiting CDK 4 and CDK 6. These 2 CDKs trigger growth and proliferation of cancer cells, particularly in hormone receptor (HR) positive, HER2-negative breast cancer cells, thus their inhibition by CDK 4/6 inhibitors causes cell cycle arrest.

Palbociclib was granted FDA approval as an initial endocrine therapy for metastatic breast cancer for use in combination with letrozole (Femara) in early 2015; in 2016, for use in combination with fulvestrant in patients who had failed prior endocrine therapy; and its original indication was expanded in 2017 to include any aromatase inhibitor (eg, anastrozole [Arimidex] or exemestane [Aromasin]). All palbociclib approvals are for women with HR-positive, HER2-negative metastatic breast cancer.

Ribociclib was granted FDA approval in 2017 as an initial endocrine therapy for women with HR-positive, HER2-negative metastatic breast cancer in combination with any aromatase inhibitor.

The efficacy of these 2 agents have not been compared head-to-head, so the decision regarding which agent to use is based upon adverse effects, formulary status, and other considerations. Both palbociclib and ribociclib are dosed once daily on a 21 days on/7 days off schedule. The adverse effects of palbocicib and ribociclib are similar, with both agents causing high rates of neutropenia (greater than 70%) as well as anemia (18% to 24%), headache (21% to 22%), and fatigue (36% to 37%) when given in combination with letrozole. Nausea has been reported in 51% of patients receiving ribociclib compared to 35% of patients receiving palbociclib, however thrombocytopenia is reported more frequently with palbociclib (15%). Additionally, elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have been reported with ribociclib.