Progression-free survival and overall survival of CDK 4/6 inhibitors plus endocrine therapy in metastatic breast cancer: A systematic review and meta-analysis

Michela Piezzo, Paolo Chiodini, Maria Riemma, Stefania Cocco, Roberta Caputo, Daniela Cianniello, Germira Di Gioia, Vincenzo Di Lauro, Francesca Di Rella, Giuseppina Fusco, Giovanni Iodice, Francesco Nuzzo, Carmen Pacilio, Matilde Pensabene, Michelino De Laurentiis

Research output: Contribution to journalReview articlepeer-review


The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).

Original languageEnglish
Article number6400
Pages (from-to)1-17
Number of pages17
JournalInternational Journal of Molecular Sciences
Issue number17
Publication statusPublished - Sep 1 2020


  • Cancer
  • CDK4/6 inhibitors
  • Epidemiology
  • Hormone receptors
  • Hormone therapy
  • Metastatic breast cancer
  • Overall survival
  • Subgroup analysis
  • Therapies

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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