Safety and Feasibility of Radiation Therapy Combined with CDK 4/6 Inhibitors in the Management of Advanced Breast Cancer

Author:

Kubeczko Marcin1ORCID,Gabryś Dorota2ORCID,Gawkowska Marzena2,Polakiewicz-Gilowska Anna1,Cortez Alexander J.3ORCID,Krzywon Aleksandra3ORCID,Woźniak Grzegorz2,Latusek Tomasz2,Leśniak Aleksandra1,Świderska Katarzyna1,Mianowska-Malec Marta1,Łanoszka Barbara1,Chomik Konstanty1,Gajek Mateusz2,Michalik Anna1,Nowicka Elżbieta4,Tarnawski Rafał4ORCID,Rutkowski Tomasz2ORCID,Jarząb Michał1ORCID

Affiliation:

1. Breast Cancer Center, Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland

2. Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland

3. Department of Biostatistics and Bioinformatics, Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland

4. III Department of Radiotherapy and Chemotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland

Abstract

The addition of CDK4/6 inhibitors to endocrine therapy in advanced hormone receptor-positive HER2-negative breast cancer has led to practice-changing improvements in overall survival. However, data concerning the safety of CDK4/6i combination with radiotherapy (RT) are conflicting. A retrospective evaluation of 288 advanced breast cancer patients (pts) treated with CDK4/6i was performed, and 100 pts also received RT. Forty-six pts received 63 RT courses concurrently and fifty-four sequentially before CDK4/6i initiation (76 RT courses). Neutropenia was common (79%) and more frequent during and after concurrent RT than sequential RT (86% vs. 76%); however, CDK4/6i dose reduction rates were similar. In patients treated with CDK4/6i alone, the dose reduction rate was 42% (79 pts) versus 38% with combined therapy, and 5% discontinued treatment due to toxicity in the combined group. The risk of CDK4/6i dose reduction was correlated with neutropenia grade, RT performed within the first two CDK4/6i cycles, and more than one concurrent RT; a tendency was observed in concurrent bone irradiation. However, on multivariate regression analysis, only ECOG 1 performance status and severe neutropenia at the beginning of the second cycle were found to be associated with a higher risk of CDK4/6i dose reduction. This largest single-center experience published to date confirmed the acceptable safety profile of the CDK4/6i and RT combination without a significantly increased toxicity compared with CDK4/6i alone. However, one might delay RT for the first two CDK4/6i cycles, when myelotoxic AE are most common.

Funder

Medical Research Agency

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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