Cyclin-dependent kinase (CDK) inhibitors have become the standard of care for the initial treatment of advanced, hormone receptor–positive breast cancer. Major phase 3 clinical trials1-6 have consistently demonstrated improved progression-free survival with the use of CDK inhibitors alone or in combination with aromatase inhibitors or fulvestrant. Cyclin-dependent kinase 4/6 inhibitors are generally well tolerated. Major adverse effects reported in clinical trials1-6 include neutropenia, fatigue, and diarrhea. However, an increased risk for venous thromboembolism (VTE) has been reported in multiple trials. Palbociclib, the first of the CDK 4/6 inhibitors to be approved by the US Food and Drug Administration (FDA), was administered with or without the aromatase inhibitor letrozole in the phase 2 PALOMA-1 trial.7 The rate of VTE was 5% in the experimental arm, while no VTE events were reported in those treated with letrozole alone.7 Positive results from this trial led to the initial FDA approval of palbociclib in 2015, with a warning against VTE; this warning was subsequently removed from the label following the larger PALOMA 2 and 3 trials, which showed a much smaller incidence of VTE.1,2
Olson SR, DeLoughery TG, Shatzel JJ. Cyclin-Dependent Kinase Inhibitor–Associated Thromboembolism. JAMA Oncol. Published online December 13, 2018. doi:10.1001/jamaoncol.2018.5529
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