The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis.

Abstract

INTRODUCTION:

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed the first-line treatment for metastatic disease with increased rates of treatment response, overall survival (OS), and progression-free survival (PFS). We performed a pooled analysis of randomized trials to validate or refute the hypothesis that there is a significant survival benefit of adding anti-CDK4/6 inhibitors to standard endocrine therapy (ET) in older patients with advanced BC.

METHODS:

We selected only English-language phase II/III randomized controlled trials that compared ET alone with ET with anti-CDK4/6 inhibitors in the treatment of advanced BC, with subgroups reporting the outcomes of elderly patients (usually at least 65 years). The primary endpoint was OS.

RESULTS:

The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials. The addition of CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced mortality risk by 20% in younger patients (fixed-effect model; HR 0.80; 95% CI 0.72-0.9; p < 0.01) and 21% in older BC patients (HR 0.79; 95% CI 0.69-0.91; p < 0.01). No OS data were available for patients ≥70 years.

CONCLUSION:

This large, pooled analysis is the first to demonstrate that CDK4/6 inhibitors confer OS and PFS benefits in elderly patients (those aged ≥65 years) with advanced ER + BC and to indicate that it should be discussed with and offered to all patients after geriatric assessment and according to the toxicity profile.

• Authors: Fausto Petrelli, Lorenzo Dottorini, Giandomenico Di Menna, Karen Borgonovo, Maria Chiara Parati, Carmen Giusy Rea, Mara Ghilardi, Antonio Ghidini, Andrea Luciani
• Journal: Breast (Edinburgh, Scotland) (Breast) Vol. 71 Pg. 138-142 (Oct 2023) ISSN: 1532-3080 [Electronic] Netherlands
• PMID: 37198053 (Publication Type: Meta-Analysis, Systematic Review, Journal Article, Review)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Cyclin-Dependent Kinase 4
• Receptor, ErbB-2
• Cyclin-Dependent Kinase 6
• Fulvestrant
• Protein Kinase Inhibitors

Topics

• Aged
• Humans
• Female
• Breast Neoplasms (pathology)
• Cyclin-Dependent Kinase 4
• Receptor, ErbB-2
• Cyclin-Dependent Kinase 6
• Fulvestrant
• Protein Kinase Inhibitors
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)