Hematological Toxicities and Febrile Neutropenia Resulting From CDK 4/6 Inhibitors

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Cyclin-dependent kinase 4/6 inhibitors may have proven benefits for treating metastatic breast cancer, but the therapies are associated with hematological toxicities and febrile neutropenia.

Inhibition of cyclin-dependent kinase (CDK) 4/6 signaling has proven benefits for the majority of breast cancers that express the estrogen receptor or progesterone receptor. However, CDK 4/6 inhibitors are associated with hematological toxicities and febrile neutropenia (FN).

An abstract presented at the American Society of Clinical Oncology’s 2017 Palliative and Supportive Care in Oncology Symposium analyzed the risk of hematological toxicities and FN in patients with breast cancer using a literature search of MEDLINE and EMBASE databases and meeting abstracts.

Studies included were randomized controlled trials that mentioned anemia, thrombocytopenia, leukopenia, neutropenia, and neutropenic fever as adverse effects. In addition, studies had to compare CDK 4/6 inhibitors based on regimen and a control group with patients with hormone receptor—positive human epidermal growth factor receptor 2 (HER-2)–negative metastatic breast cancer.


The meta-analysis included 5 trials with 2671 patients total, with 4 of the studies in phase 3 and the other in phase 2.

The study arms used palbociclib-letrozole, palbociclib-fulvestrant, ribociclib-letrozole, and abemaciclib-fulvestrant, and the control arms used placebo with either letrozole or fulvestrant. The analysis found that the pooled risk of neutropenic fever was statistically significant at 4.26.

The relative risks of all-grade side effects were:

  • Anemia, 3.77
  • Thrombocytopenia, 9.69
  • Leukopenia, 11.68
  • Neutropenia, 14.09

The relative risks of high-grade adverse effects were:

  • Anemia, 2.55
  • Thrombocytopenia, 7.08
  • Leukopenia, 33.58
  • Neutropenia, 40.33

“CDK 4/6 inhibitors based regimen significantly contributed to all hematological toxicities as well as febrile neutropenia,” the authors concluded. “These toxicities affect patients’ quality of life, add financial burden and may lead to drug dosing inconsistencies.”