Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors combined with letrozole or fulvestrant substantially prolong progression-free survival (PFS) with a well-tolerated, predictable safety profile. Understanding the safety profile of selective CDK4/6 inhibitors can inform adverse event (AE) management and can extend and maintain time on treatment. Here, we report common AEs associated with CDK4/6 inhibitors and perspectives on monitoring as well as managing these AEs. Methods: We reviewed 5 published Phase II/III trials of ≥50 patients with advanced breast cancer (ABC) treated with CDK4/6 inhibitors in combination with endocrine therapy with respect to commonly reported AEs, defined as AEs reported in ≥15% (any grade) or ≥5% (Grade 3/4) of patients in ≥4 of 5 trials. Results: The most common AEs consisted of hematologic, gastrointestinal, and general well-being AEs (Table). Nonhematologic AEs were mostly Grade ≤2 and easily managed with dose modification. Uncomplicated neutropenia was the most common hematologic AE and was noncumulative, with the lowest neutrophil counts typically reached within a month of initiating treatment, and did not require intervention. Median time to resolution of Grade 3 neutropenia was 7–15 days. Febrile neutropenia was rare (<2%). Conclusions: CDK4/6 inhibitors are characterized by early, predictable, easily managed, transient AEs that do not require intervention. Awareness of and patient support for these AEs can enable patients with ABC to remain on CDK4/6 treatment and achieve associated PFS benefits.

AE, adverse event. ^a Including palbociclib + letrozole (n=2), palbociclib + fulvestrant (n=1), ribociclib + letrozole (n=1), and abemaciclib + fulvestrant (n=1). ^bIncluding placebo + letrozole (n=3) and placebo + fulvestrant (n=2).