Safety profile of cyclin-dependent kinase (CDK) 4/6 inhibitors with concurrent radiation therapy: A systematic review and meta-analysis

Carlotta Becherini, Luca Visani, Saverio Caini, Indrani S. Bhattacharya, Anna M. Kirby, Gustavo Nader Marta, Gilberto Morgan, Viola Salvestrini, Charlotte E. Coles, Javier Cortes, Giuseppe Curigliano, Evandro de Azambuja, Nadia Harbeck, Clare M. Isacke, Orit Kaidar-Person, Elisabetta Marangoni, Birgitte Offersen, Hope S. Rugo, Andrea Morandi, Matteo LambertiniPhilip Poortmans, Lorenzo Livi, Icro Meattini*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the standard of care for hormone receptor-positive (HR + ) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer, improving survival outcomes compared to endocrine therapy alone. Abemaciclib and ribociclib, in combination with endocrine therapy, have demonstrated significant benefits in invasive disease-free survival for high-risk HR+/HER2- early breast cancer patients. Each CDK4/6i—palbociclib, ribociclib, and abemaciclib—exhibits distinct toxicity profiles. Radiation therapy (RT) can be delivered with a palliative or ablative intent, particularly using stereotactic body radiation therapy for oligometastatic or oligoprogressive disease. However, pivotal randomized trials lack information on concomitant CDK4/6i and RT, and existing preclinical and clinical data on the potential combined toxicities are limited and conflicting. As part of a broader effort to establish international consensus recommendations for integrating RT and targeted agents in breast cancer treatment, we conducted a systematic review and meta-analysis to evaluate the safety profile of combining CDK4/6i with palliative and ablative RT in both metastatic and early breast cancer settings.
Original languageEnglish
Article number102586
Number of pages11
JournalCancer Treatment Reviews
Volume119
Issue number1
DOIs
Publication statusPublished - 1 Sept 2023

Keywords

  • Breast cancer
  • CDK4/6 inhibitors
  • Meta-analysis
  • Radiotherapy
  • Systematic review
  • Toxicity

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