Safety of CDK4/6 inhibitors and concomitant radiation therapy in patients affected by metastatic breast cancer. (December 2022)

• Record Type: Journal Article
• Authors: Visani, Luca; Livi, Lorenzo; Ratosa, Ivica; Orazem, Miha; Ribnikar, Domen; Saieva, Calogero; Becherini, Carlotta; Salvestrini, Viola; Scoccimarro, Erika; Valzano, Marianna; Cerbai, Cecilia; Desideri, Isacco; Bernini, Marco; Orzalesi, Lorenzo; Nori, Jacopo; Bianchi, Simonetta; Morandi, Andrea; Meattini, Icro
• Is Part Of: Radiotherapy and oncology. Volume 177(2022)
• Page Start: 40
• Page End: 45
• Publication Date: 2022-12
• Subjects: Breast cancer -- Radiotherapy -- CDK4/6 inhibitors -- Oligometastatic disease -- Concomitant treatment; CDK4/6i Cyclin-Dependent Kinase 4/6 inhibitors -- RT Radiation Therapy -- 3DCRT Three-Dimensional Conformal Radiation Therapy -- VMAT Volumetric Modulated Arc Therapy -- IMRT Intensity Modulated Radiation Therapy -- SBRT Stereotactic Body Radiation Therapy -- SRS Stereotactic Radiosurgery -- HT Helical Tomotherapy -- NA not available -- OR odds ratio -- CI confidence interval -- HR hazard ration -- MBC metastatic breast cancer -- HR+/HER2- hormone receptor-positive/ human epidermal growth factor receptor 2-negative -- AEs adverse events -- PFS progression-free survival -- OS overall survival -- CT chemotherapy -- ET endocrine therapy -- ≥G3 grade 3 or higher -- CTCAE Common Terminology Criteria for Adverse Events -- EORTC European Organization for Research and Treatment of Cancer -- ESTRO European Society for Radiotherapy -- SD standard deviation -- ER oestrogen receptor -- PgR progesterone receptor; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2022.10.023
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: CDK4/6 inhibitors represent the standard-of-care for metastatic HR+/HER2 breast cancer. Available data on CDK4/6 inhibitors and concomitant RT are conflicting. We showed that concurrent RT did not increase treatments severe toxicity. A consensus guideline to help physician's routine practice is strongly needed. Abstract: Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) currently represent the standard of care for the initial treatment of patients with metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. The aim of our study is to evaluate the safety of the use of concomitant radiation therapy (RT) in a consecutive series of HR+/HER2- patients treated in two academic institutions with CDK4/6i in the metastatic setting. Methods and materials: From September 2017 to February 2020, we retrospectively collected and analysed data on a sequential series of patients treated with CDK4/6i, receiving RT or not, at two European institutions. Primary outcome of the study was the association between RT and any adverse events (AEs) ≥ G3. Secondary outcomes were the association between RT and any AEs (any grade), CDK4/6i dose reduction rate, and CDK4/6i treatment discontinuation rate. Results: We analysed a total of 132 consecutive women; RT was prescribed in 57 (43.2%) patients (70 irradiated lesions). The median age of the series was 52.1 years (range 32.3–78.2). Concomitant RT administration was not significantly related to higher AEs ≥ G3 (p = 0.19) and any grade AEs (p = 1.0); there was no association with RT and CDK4/6i dose reduction (p = 0.49) and discontinuation rates (p = 0.14). At a median follow-up of 18.8 months, the progression-free survival (PFS) rate was 35% and the overall survival (OS) rate was 38.7% in the whole group. The use of concomitant RT did not affect both PFS (p = 0.71) and OS rates (p = 0.55). Conclusions: Our data are encouraging regarding the safety of this combination, showing that concurrent RT did not increase severe toxicity and did not have an impact on systemic treatment conduction.