CDK4/6 Inhibitors Plus Radiotherapy for Patients With HR+/HER2– Advanced Breast Cancer With Brain Metastases

For patients with hormone receptor-positive, HER2-negative (HR+/ HER2–) advanced breast cancer, cyclin-dependent kinase 4/6 inhibitors (CKD4/6i) + endocrine therapy is the first- and second-line treatment of choice. Although metastasis to the brain generally is not found at the beginning of treatment for this type of cancer it can be found later during the disease course and with other types of breast cancer. To determine the efficacy and safety of CKD4/6i and radiotherapy for the treatment of brain metastases in patients with HR+/HER2– advanced breast cancer, a retrospective analysis was performed. Two groups were compared during the study. Group 1 included patients who received radiotherapy concurrently with CDK4/6i or radiotherapy before beginning CDK4/6i therapy. Group 2 included patients who experienced brain metastasis during CDK4/6i treatment and then were treated with radiotherapy. The study primary end point was progression-free survival (PFS) with secondary endpoints of local control of cancer in the brain and treatment toxicity.

There were 379 patients in the analysis who received CDK4/6i with 26 patients treated with radiotherapy to the brain. The median age of the patients was 51.5 years with a range of 41-62 years. De novo metastatic disease was found in 6 patients. When Eastern Cooperative Oncology Group (ECOG) performance status was examined, 6 patients had ECOG performance status of 0, 15 patients had ECOG performance status of 1, while 5 patients had ECOG performance status of 2. There were 15 patients who were treated in the first-line setting. Radiotherapy before or concurrent with CDK4/6i treatment was received by 17 patients and these patients were included in Group 1. The remaining 9 patients received radiotherapy after treatment with CDK4/6i due to disease progression and were in Group 2. Ribociclib was used by 17 patients, palbociclib was used by 7 patients, and 2 patients received abemaciclib. The endocrine therapy used by 15 patients was letrozole while 11 patients received fulvestrant. Whole-brain radiotherapy with a total dose of 20 Gy delivered in 5 fractions was received by 11 patients and 8 patients received stereotactic radiation therapy. In Group 1, the 6-month progression-free survival (PFS) was 88.2% and the 12-month PFS was 58.8%. In Group 2, the 6-month PFS was 55.6% and the 12-month PFS was 44.4%. Local control at 6 months for Group 1 was 92.3% while 12-month local control was 83.9%. In Group 2, local control at 3 months was 66.7%. No unanticipated toxicity was reported at a median follow-up of 8.8 months.

Source:

Kubeczko M, Gabrys D, Polakiewicz-Gilowska A, et al. Cyclin-dependent kinase 4/6 inhibitors combined with radiotherapy in the management of brain metastases in HR-positive/HER2-negativebreast cancer patients. Poster presented at: San Antonio Breast Cancer Symposium. December 6, 2023; San Antonio, TX. Abstract # PO1-05-01.