Pharmacokinetic drug evaluation of abemaciclib for advanced breast cancer

ABSTRACT

Introduction: The combination of cyclin-dependent kinases 4 and 6 (CDK 4 and 6) inhibitors with endocrine therapy represents a new standard of care for endocrine-receptor positive metastatic breast cancer. Currently, three compounds are approved. Abemaciclib is the latest CDK4/6 inhibitor approved by the US Food and Drug Administration in view of the results of the MONARCH1 and 2 trials.

Area covered: In this article, we review the preclinical and clinical development of abemaciclib in advanced breast cancer, describing current therapeutic indications and open questions.

Expert opinion: Results of phase III trials investigating abemaciclib in patients with endocrine-receptor positive metastatic breast cancer have shown a substantial improvement in progression-free-survival, with a safe and manageable toxicity profile. In order to better select patients who will more likely respond to CDK4/6 inhibitors, biomarkers need to be identified. To optimize CDK4/6 targeting, combination therapies are being tested in several ongoing trials.

KEYWORDS:

• Metastatic breast cancer
• CDK4/6 inhibitors
• cell-cycle regulation
• abemaciclib

Table

Declaration of interest

M Campone reports conflicts of interest with Pfizer, Lilly, Astra Zeneca, Novartis (Board member), Pierre Fabre and Sanofi (consultancy). JS Frenel declares conflicts of interest with Pfizer, Roche, Astra Zeneca (Board member and travel fees). P Augereau declares conflicts of interest with Pfizer, Astra Zeneca, and Novartis. M Robert reports conflicts of interest with Amgen, Merck, and Novartis (travel fees and honoraria). A Patsouris declares conflicts of interest with Roche, Eisai, and Pfizer (travel fees). E Bourbouloux declares conflicts of interest with Amgen (travel fees). 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.

Reviewer disclosures

One peer reviewer has served on advisory board for Pfizer (palbociclib), Novartis (ribociclib) and Eli Lilly (abemaciclib). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.