The efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in the adjuvant treatment of patients with high-risk invasive HR+/HER2-early breast cancer: A comprehensive updated meta-analysis of randomized clinical trials

Breast. 2024 Dec:78:103815. doi: 10.1016/j.breast.2024.103815. Epub 2024 Oct 15.

Abstract

Background: This paper aimed to evaluate the effectiveness of incorporating CDK 4/6 inhibitors (CDK4/6i) into ET for the adjuvant treatment of HR + HER2-resected early-stage breast cancer (ESBC) patients, employing meta-analysis.

Methods: In this paper, we compiled randomized clinical trials focusing on CDK4/6i used in the adjuvant treatment of high-risk invasive HR-positive and HER2-ESBC patients. A meta-analysis was performed in line with the PRISMA guidelines.

Results: We identified four clinical trials that met our inclusion criteria and were published between 2020 and 2024. These trials involved a combined sample size of 17,749 patients diagnosed with breast cancer. The data obtained from the pooled analysis revealed a remarkable beneficial trend in terms of invasive disease-free survival (iDFS) for the use of ET in combination with CDK4/6i compared to the group receiving ET alone (HR = 0.81, 95 % CI: 0.67-0.98, p = 0.03). Of note, CDK4/6 inhibitors demonstrated a notably beneficial effect in both grade 2 (HR = 0.69, 95 % CI: 0.59-0.81, p < 0.001) and grade 3 (HR = 0.76, 95 % CI: 0.65-0.89, p < 0.001). Significant improvements were noted in terms of distant relapse-free survival (dRFS) in the groups treated with abemaciclib and ribociclib (HR = 0.65, 95 % CI: 0.56-0.76, p < 0.001; HR = 0.72, 95 % CI: 0.58-0.89, p = 0.003, respectively). CDK4/6i didn't yield a statistically significant difference in overall survival (OS) (HR = 0.96, 95 % CI: 0.77-1.19, p = 0.69). The use of CDK4/6i with ET was associated with an increased risk of adverse events, particularly anemia and neutropenia, compared with ET alone (OR = 9.12, 95 % CI = 5.04-16.48, p < 0.001).

Conclusion: The findings of this paper demonstrate a significant improvement in iDFS when ET is combined with CDK4/6i, compared to ET alone. Specifically, treatments with abemaciclib and ribociclib showed notable enhancements in dRFS.

Keywords: Abemaciclib; CDK4/6 inhibitor; Meta-analysis; Palbociclib; Ribociclib.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aminopyridines / administration & dosage
  • Aminopyridines / therapeutic use
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Benzimidazoles
  • Breast Neoplasms* / drug therapy
  • Chemotherapy, Adjuvant
  • Cyclin-Dependent Kinase 4* / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6* / antagonists & inhibitors
  • Disease-Free Survival
  • Female
  • Humans
  • Middle Aged
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Purines / administration & dosage
  • Purines / therapeutic use
  • Randomized Controlled Trials as Topic*
  • Receptor, ErbB-2* / metabolism
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism

Substances

  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Receptor, ErbB-2
  • CDK4 protein, human
  • CDK6 protein, human
  • Antineoplastic Agents, Hormonal
  • Protein Kinase Inhibitors
  • Aminopyridines
  • ERBB2 protein, human
  • ribociclib
  • abemaciclib
  • Purines
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Benzimidazoles