Use of cyclin-dependent kinase (CDK) 4/6 inhibitors for hormone receptor-positive, human epidermal growth factor receptor 2-negative, metastatic breast cancer: a roundtable discussion by The Breast Cancer Therapy Expert Group (BCTEG).

Abstract

PURPOSE:

To provide an overview of clinical data supporting the use of cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), metastatic breast cancer (mBC), from the perspective of the practicing oncologist community.

METHODS:

A recent roundtable discussion was convened by The Breast Cancer Therapy Expert Group (BCTEG) to review existing data on this topic and its impact on their current practice.

RESULTS:

Level 1 evidence now supports use of a CDK 4/6 inhibitor in combination with endocrine therapy for patients with HR+, HER2-, mBC. Currently, there are no biomarkers that reliably define patients who will, or will not, benefit from the addition of a CDK 4/6 inhibitor to their endocrine therapy. Additional research is needed to identify the optimal sequencing of CDK 4/6 inhibitors in relation to other therapies as well as the optimal duration of therapy; at present, evidence suggests that use in the upfront setting is better than waiting for a later line of therapy, or adding after endocrine therapy has started.

CONCLUSIONS:

Thus far, three CDK 4/6 inhibitors-palbociclib, ribociclib, and more recently, abemaciclib-have been approved for use in the setting of HR+, HER2-, mBC.  The degrees to which these agents differ in terms of CDK4/6 affinity, side-effect profiles, dosing, degree of central nervous system (CNS) penetration, optimal use in combination with antiestrogen therapy, and across other subsets of breast cancer, remain an active area of investigation.

• Authors: Jame Abraham, Robert Coleman, Anthony Elias, Frankie Ann Holmes, Kevin Kalinsky, Muaiad Kittaneh, Elyse Lower, Reshma Mahtani, E Terry Mamounas, Mark Pegram, Charles Vogel, Breast Cancer Therapy Expert Group (BCTEG)
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 171 Issue 1 Pg. 11-20 (Aug 2018) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 29725889 (Publication Type: Journal Article, Review)

Chemical References

• Biomarkers
• Protein Kinase Inhibitors
• Receptors, Estrogen
• Receptors, Progesterone
• Receptor, ErbB-2
• CDK4 protein, human
• CDK6 protein, human
• Cyclin-Dependent Kinase 4
• Cyclin-Dependent Kinase 6

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers
• Breast Neoplasms (drug therapy, metabolism, mortality, pathology)
• Cyclin-Dependent Kinase 4 (antagonists & inhibitors)
• Cyclin-Dependent Kinase 6 (antagonists & inhibitors)
• Female
• Humans
• Molecular Targeted Therapy
• Neoplasm Metastasis
• Neoplasm Staging
• Protein Kinase Inhibitors (pharmacology)
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)