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 Bhattacharya, Anna M. Kirby, Gustavo Nader Marta, Gilberto Morgan, Viola Salvestrini, Charlotte E. Coles, Javier Cortés, Giuseppe Curigliano, Evandro de Azambuja, Nadia Harbeck, Clare M. Isacke, Orit Kaidar‐Person, Elisabetta Marangoni, Birgitte Vrou Offersen, Hope S. Rugo, Andrea Morandi, Matteo Lambertini, Philip Poortmans, Lorenzo Livi, Icro Meattini
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.