An evaluation of palbociclib as a breast cancer treatment option: a current update

ABSTRACT

Introduction

Patients with hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer have benefitted from treatment with palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor capable of selectively targeting mechanisms of cell cycle progression that contribute to tumor cell proliferation. Palbociclib use in this setting demonstrates improved progression-free survival when given in combination with aromatase inhibitors or fulvestrant.

Areas covered

The authors describe the current state of research surrounding palbociclib use in breast cancer, present evidence supporting a role for palbociclib in additional subtypes of metastatic breast cancer such as HER2-positive (HER2+) and triple-negative, report ongoing clinical trials aimed at expanding the scope of use for palbociclib, and discuss expected clinical results that will better inform decisions on including palbociclib as a part of breast cancer treatment strategies.

Expert opinion

Preclinical and clinical studies have shown promising evidence for palbociclib use in metastatic HER2+ and androgen receptor-expressing triple-negative breast cancer but mixed results in the adjuvant/neoadjuvant setting, where differences may only be detectable in high-risk disease. Palbociclib combinations may constitute viable replacements for chemotherapy in the neoadjuvant setting as part of de-escalation strategies. Investigation into synergy of palbociclib with immunotherapies is also ongoing based on non-canonical effects of CDK4/6 inhibition on the tumor immune microenvironment.

KEYWORDS:

• Adjuvant therapy
• breast cancer
• CDK4/6 inhibitors
• clinical trials
• metastatic breast cancer
• neoadjuvant therapy
• palbociclib
• triple-negative breast cancer
• HER2-positive breast cancer
• HR+HER2- breast cancer

Article highlights

• Palbociclib is well-established in the treatment of HR+/HER2- metastatic breast cancer as first-line therapy in combination with letrozole or as second-line therapy with fulvestrant.

• Several clinical trials are currently exploring an expanded role for palbociclib as part of targeted therapy combinations in other subtypes of metastatic breast cancer, with promising results in HER2+ and androgen receptor-positive triple-negative breast cancers.

• Neoadjuvant palbociclib use in early invasive breast cancer is also under investigation in a number of clinical trials, and preliminary results demonstrate equivalent decreases in tumor cell proliferation markers with fewer adverse events compared to chemotherapy.

This box summarizes key points contained in the article.

Declaration of interest

GT Gallanis was supported by a National Institutes of Health (NIH)/National Cancer Institute (NCI) grant T32 CA009686 while AT Riegel was supported by NIH/NCI grants RO1 CA205632, R21 C226542 and T32CA009686. PR Pohlmann meanwhile has received research funding via their institution from Genentech/Roche, Pfizer Inc, Seattle Genetics and Cascadian Therapeutics. She has also served on the speaker’s bureau of Genentech/Roche. 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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Gregory T. Gallanis  received support from NIH/NCI T32 CA009686; Anna T. Riegel received support from NIH/NCI R01 CA205632, NIH/NCI R21 CA226542, and NIH/NCI T32 CA009686.