Difference Between CDK Inhibitors

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CDK inhibitors work by inhibiting the two CDKs that trigger growth and expansion of cancer cells.
CDK inhibitors work by inhibiting the two CDKs that trigger growth and expansion of cancer cells.

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.

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