Palbociclib and beyond for the treatment of HR + HER2- metastatic breast cancer: an Asian-Pacific perspective and practical management guide on the use of CDK4/6 inhibitors

Abstract

Breast cancer is the most frequent cancer amongst women worldwide including in Asia where the incidence rate is rapidly increasing. Even with treatment, around 30% of patients with early breast cancer progress to metastatic disease, with hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer the most common phenotype. First-line endocrine therapy targeting the estrogen receptor signaling pathway provides a median progression-free survival or time to progression of 6–15 months in HR + HER2- metastatic breast cancer. Recently, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, combined with endocrine therapy, have achieved more than two years median progression-free survival in HR + HER2- metastatic breast cancer. However, the characteristics of the Asian breast cancer population differ from those of Western populations and need to be considered when selecting a suitable treatment. Breast cancer is diagnosed at a younger age in Asian populations and late stage at presentation is generally more common in low-/middle-income countries than high-income countries. Consequently, the proportion of premenopausal women with metastatic breast cancer is higher in Asian compared with Western populations. While CDK4/6 inhibitors have been approved in the USA (FDA) since 2015, experience with them in Asia is more limited. We review the experience with the CDK4/6 inhibitor palbociclib in Asian patients with HR + HER2- metastatic breast cancer and provide guidance on the use of palbociclib in these patients.

Keywords:

• Breast cancer
• CDK4/6 inhibitor
• palbociclib
• practical guidance
• endocrine therapy
• hormone receptor positive
• Asia Pacific

Transparency

Declaration of funding

There was no sponsorship/funding of this work apart from that noted in the acknowledgements below.

Declaration of financial/other relationships

SD has received honoraria from Novartis, Pfizer, Roche and Bristol-Myers Squibb. JWC has received honoraria and travel support for scientific conferences from Pfizer. C-SH has received a consulting fee (advisory board) and an honorarium (invited speaker) from Pfizer. Dr Huang’s institute has received contracted research funding from Pfizer. SN has no relevant conflicts of interest to declare. AS has received honoraria from Pfizer, AstraZeneca, Roche, Eli Lilly, Boehringer Ingelheim and Novartis (invited speaker, advisory boards). YSY has provided consultancy to, and received honoraria and travel support from, Pfizer. MMY has received honoraria from Roche, AstraZeneca Eli Lilly, Novartis and Pfizer. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no other relevant financial relationships to disclose.

Author contributions

All the authors were involved in the conception, design and critical review of this paper, including the final approval of this version, and agree to be accountable for all aspects of this work.

Acknowledgements

The authors thank Pfizer and Linda Crofts (BSc, PhD), of McCann Health, Sydney, Australia who provided medical writing support funded by Pfizer Emerging Asia. Pfizer Emerging Asia did not influence the content or development of the manuscript.