Quantitative evaluation of the efficacy and safety profiles of two types of targeted inhibitors combined with endocrine therapy in ER+/HER2- metastatic breast cancer

Eur J Clin Pharmacol. 2024 Sep;80(9):1387-1397. doi: 10.1007/s00228-024-03715-4. Epub 2024 Jun 20.

Abstract

Purpose: The aim of this study was to quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2- metastatic breast cancer.

Methods: A parametric survival function was used to analyze the time course of overall survival (OS) and progression-free survival (PFS). The objective response rate (ORR) and the incidence of any grade and grade 3-4 adverse events were summarized using the random-effects model of a single-arm meta-analysis.

Results: This study included 44 arms from 48 publications, with a total sample size of 7881 patients. Our study revealed that CDK4/6 inhibitors had a median OS of 40.7 months, a median PFS of 14.8 months, and an ORR of 40%, whereas PI3K/AKT/mTOR inhibitors had a median OS of 29.8 months, a median PFS of 8.3 months, and an ORR of 20%. Additionally, this study also found that the proportion of patients with visceral metastases and specific endocrine therapy used in combination significantly impact OS and PFS. In terms of adverse events, CDK4/6 inhibitors exhibited a relatively high incidence of hematological adverse events.

Conclusion: Our study provides solid quantitative evidence for the first-line recommendation of CDK4/6 inhibitors combined with endocrine therapy for ER+/HER2- metastatic breast cancer in clinical guidelines.

Keywords: CDK4/6 inhibitors; ER+/HER2− metastatic breast cancer; Efficacy; Influencing factors; Model-based meta-analysis; OS; PFS; PI3K/AKT/mTOR inhibitors.

Publication types

  • Meta-Analysis

MeSH terms

  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Cyclin-Dependent Kinase 4* / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6* / antagonists & inhibitors
  • Female
  • Humans
  • Neoplasm Metastasis
  • Phosphoinositide-3 Kinase Inhibitors / administration & dosage
  • Phosphoinositide-3 Kinase Inhibitors / therapeutic use
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, ErbB-2* / antagonists & inhibitors
  • Receptor, ErbB-2* / metabolism
  • Receptors, Estrogen / metabolism
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Receptor, ErbB-2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • ERBB2 protein, human
  • TOR Serine-Threonine Kinases
  • Receptors, Estrogen
  • Protein Kinase Inhibitors
  • MTOR protein, human
  • CDK4 protein, human
  • Proto-Oncogene Proteins c-akt
  • CDK6 protein, human
  • Antineoplastic Agents, Hormonal
  • Phosphoinositide-3 Kinase Inhibitors