Abemaciclib for the treatment of HR+/HER2- breast cancer

ABSTRACT

Introduction: More than 70% of patients with advanced breast cancer have hormone receptor (HR)-positive disease and almost all patients will develop resistance to endocrine agents and experience disease progression. CDK 4/6 inhibitors represent a new paradigm shift in treatment for patients with endocrine resistance. Also, its use as front-line therapy reached unprecedented progression-free survival rates in these patients. Currently, there are 3 CDK 4/6 inhibitors available: ribociclib, palbociclib and abemaciclib.

Areas covered: In this review, the authors analyze abemaciclib from its pre-clinical development until recent randomized phase III trials, which led to the approval and use of this extremely relevant drug in the treatment of HR-positive breast cancer. The authors also discuss abemaciclib’s different adverse events profile compared to similar drugs and its potential role as monotherapy and as treatment for brain metastasis.

Expert commentary: Abemaciclib is an important advance in the treatment of metastatic HR-positive/HER2-negative breast cancer, and data support its use in combination with endocrine therapy for first- and second-line therapy for metastatic disease, and its unique efficacy as monotherapy and for CNS metastasis. Molecular biomarkers, combination therapy with other agents, and the best sequence for treatment are under investigation and should clarify how to optimize treatment for each patient.

KEYWORDS:

• Breast cancer
• hormonal receptor positive
• abemaciclib
• CDK 4/6 inhibitors
• LY2835219
• endocrine resistance
• cyclin-dependent kinase

Information resources

A PubMed search using the following keywords was performed: Abemaciclib, CDK 4/6 inhibitors, LY2835219. Also, clinicaltrials.gov were accessed for ongoing trials. Previous abstract of Annual Meeting of American Society of Clinical Oncology and San Antonio Breast Cancer Symposium Meeting were also accessed.

Acknowledgments

The authors kindly thank Kaitlyn T. Bifolck for her editorial support to this work.

Declaration of interest

SM Tolaney receives research funding (institutional) from Eli Lilly, Pfizer, Novartis, AstraZeneca, Merck, Bristol Meyers Squibb, Exelixis, Eisai, and Nektar; she has also served as an advisor to Eli Lilly, Pfizer, Novartis, AstraZeneca, Merck, Eisai, Nektar, Puma, Genentech, and Nanostring. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.