CDK4/6 Inhibitors in Hormone Receptor-Positive Metastatic Breast Cancer: Current Practice and Knowledge

Abstract

Treatment paradigms in advanced hormone receptor (HR)-positive breast cancer were substantially transformed with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) approval. The addition of these drugs to endocrine treatment profoundly improved progression-free and overall survival. Additionally, other important endpoints, such as the response rate, time to chemotherapy, and a delay in quality of life deterioration, were positively impacted by CDK4/6 inhibitors’ addition to the treatment of advanced HR-positive breast cancer. This review article will summarize current knowledge on CDK4/6 inhibitors in clinical practice for advanced HR-positive metastatic breast cancer, as well as describe recent efforts to more precisely characterize mechanisms of sensitivity and resistance to these drugs, both on the molecular and clinical characterization level.

[18F]-Fluorodeoxyglucose Positron Emission Tomography/CT to Assess the Early Metabolic Response in Patients with Hormone Receptor-Positive HER2-Negative Metastasized Breast Cancer Treated with Cyclin-Dependent 4/6 Kinase Inhibitors

“…Currently there is no tool for early response assessment in patients with metastasized breast cancer undergoing CDK4/6 inhibitor therapy. Depending on the treatment line and the presence of visceral metastasis or endocrine resistance, the median PFS is <10 months, with up to 40% of patients having PD during the first 6 months of treatment [10, 16]. Moreover, CDK4/6 inhibitor therapy causes significant adverse reactions and high treatment costs, making early response assessment an important clinical issue.…”

“…However, it remains unclear which patients will benefit from CDK4/6 inhibitor therapy. Predicting the response to CDK4/6 inhibitor therapy is of great importance given the high rate of side effects like neutropenia, diarrhea, and alopecia, the high treatment costs, and the possibility of initiating alternative therapy at an early time point [10].…”

A mixed‐methods study of cyclin‐dependent kinase 4 and 6 inhibitor symptom burden and quality of life among metastatic breast cancer patients and providers

“…This is consistent with AE reports from clinical trials. 37 Surveys indicated that patients’ average total symptom burden was slightly to moderately bothersome, and average fatigue scores exceeded the cutoff for severe fatigue. 33 Of note, it may not always be possible for patients to tease apart symptoms caused by their disease versus CDK4/6 inhibitors versus other treatments such as endocrine therapy.…”

Adjuvant abemaciclib‑induced pneumonitis: A case report and review of the literature

“…The activation of cyclin-dependent kinases (CDKs) enables cell cycle progression, representing the hallmark of cancer pathological development. The most important drivers of cell cycle proliferation are known to be CDK4/6 (3). Recently, the US Food and Drug Administration, the European Medicine Agency and the Saudi Food and Drug Administration (SFDA), approved three highly selective inhibitors of CDK4/6 for (HR + /HER2 -) advanced metastatic breast cancer, namely (palbociclib, ribociclib and abemaciclib) (4)(5)(6)(7)(8)(9)(10)(11)(12).…”