Comparative Efficacy of CDK4/6 Inhibitors Plus Aromatase Inhibitors Versus Fulvestrant for the First-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer: A Network Meta-Analysis

Target Oncol. 2019 Apr;14(2):139-148. doi: 10.1007/s11523-019-00633-9.

Abstract

Background: Several endocrine therapies are available for postmenopausal women with hormone receptor-positive (HR +) advanced breast cancer (ABC). Given the absence of direct comparisons between fulvestrant and cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with aromatase inhibitors (AIs), which are both used as standard first-line treatments for ABC, an indirect comparison using a network meta-analysis may be advantageous for decision making.

Objective: We performed a network meta-analysis to compare the efficacies of fulvestrant and CDK4/6is plus AIs as the first-line treatment of postmenopausal breast cancer patients.

Patients and methods: In order to compare these treatments, we searched the PubMed, Cochrane Library, and EMBASE databases for randomized controlled trials of first-line endocrine treatment for advanced or metastatic breast cancer until October 2018. We included a total of 11 eligible trials with 5448 patients. The hazard ratios (HRs) for the efficacies of the different treatments were used as inputs in the network meta-analysis.

Results: In the overall analysis, CDK4/6is plus AIs, including palbociclib plus letrozole, ribociclib plus letrozole, and abemaciclib plus nonsteroidal AI (letrozole or anastrozole), are all superior to 500 mg fulvestrant (HR = 0.50, 95% confidence interval [CI] 0.37-0.68; HR = 0.50, 95% CI 0.35-0.71; and HR = 0.49, 95% CI 0.34-0.71; respectively).

Conclusions: Within the limitations of this network meta-analysis, the comparison indicates that CDK4/6is plus AIs might represent a better option for HR+ ABC as a first-line endocrine treatment compared with fulvestrant.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Aminopyridines / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzimidazoles / administration & dosage
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Clinical Trials as Topic
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
  • Female
  • Fulvestrant / administration & dosage
  • Humans
  • Letrozole / administration & dosage
  • Network Meta-Analysis
  • Piperazines / administration & dosage
  • Purines / administration & dosage
  • Pyridines / administration & dosage
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism

Substances

  • Aminopyridines
  • Benzimidazoles
  • Biomarkers, Tumor
  • Piperazines
  • Purines
  • Pyridines
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Fulvestrant
  • abemaciclib
  • Letrozole
  • Receptor, ErbB-2
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • palbociclib
  • ribociclib