Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials

  • Fausto PetrelliEmail author
  • Antonio Ghidini
  • Rebecca Pedersini
  • Mary Cabiddu
  • Karen Borgonovo
  • Maria Chiara Parati
  • Mara Ghilardi
  • Vito Amoroso
  • Alfredo Berruti
  • Sandro Barni



Several trials have demonstrated the benefit of anti-CDK4/6 inhibitors plus endocrine therapy in estrogen receptor-positive (ER+) advanced breast cancer (BC), in first or subsequent lines of therapy. However, due to the lack of direct/indirect comparisons, there are no data demonstrating the superiority of one drug over the other. We compared the effectiveness of palbociclib, ribociclib, and abemaciclib in advanced ER + BC via an indirect adjusted analysis.


We performed electronic searches in the PubMed, EMBASE, and Cochrane databases for prospective phase 3 randomized trials evaluating anti-CDK4/6 inhibitors plus endocrine agents. We compared the results with an adjusted indirect analysis of randomized-controlled trials. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR) and G3–4 toxicities occurring in ≥ 5% of patients.


Six trials and six treatment arms including a total of 3743 participants, were included. For PFS and ORR analysis, the three agents were similar in both first- and second-line studies. All G3–4 toxicities were similar, with reduced risk of diarrhea for palbociclib versus abemaciclib (relative risk [RR] 0.13, 95% CI 0.02–0.92; P = 0.04) and of QTc prolongation for palbociclib versus ribociclib (RR 0.02, 95% CI 0–0.83; P = 0.03). Despite different inclusion criteria and length of follow-up, similar features were noticed among second-line studies with the exception of increased risk of anemia G3–4 and diarrhea G3–4 for abemaciclib.


Based on PFS and ORR results of this indirect meta-analysis, palbociclib, ribociclib, and abemaciclib are equally effective in either first- or second-line therapy for advanced ER + BC. They, however, ported different toxicity profiles.


Breast cancer CDK-4/6 inhibitors Meta-analysis 


Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants performed by any of the authors.

Informed consent

Not applicable (no informed consent required).

Supplementary material

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Supplementary material 1 (DOCX 18 KB)
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Supplementary material 2 (DOCX 14 KB)
10549_2019_5133_MOESM3_ESM.docx (18 kb)
Supplementary material 3 (DOCX 17 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Fausto Petrelli
    • 1
    Email author
  • Antonio Ghidini
    • 2
  • Rebecca Pedersini
    • 3
  • Mary Cabiddu
    • 1
  • Karen Borgonovo
    • 1
  • Maria Chiara Parati
    • 1
  • Mara Ghilardi
    • 1
  • Vito Amoroso
    • 3
  • Alfredo Berruti
    • 3
  • Sandro Barni
    • 1
  1. 1.Medical Oncology UnitASST Bergamo OvestTreviglioItaly
  2. 2.Medical Oncology UnitCasa di Cura IgeaMilanItaly
  3. 3.Breast UnitASST Spedali CiviliBresciaItaly

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