CDK inhibitors and radiation therapy in breast cancer: Hematologic toxicity and survival implications.

Abstract

e15095 Background: Breast cancer is the most common cancer and the second leading cause of cancer-related deaths in women. Hormone receptor-positive, HER2-negative breast cancer is treated with endocrine agents, but resistance develops, necessitating cytotoxic agents.Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) halt cell cycle progression, interrupting cancer cell proliferation. Recently, palbociclib, ribociclib, and abemaciclib have been approved with endocrine therapy for HR+ HER2- locally advanced or metastatic breast cancer. CDK4/6i frequently cause hematologic side effects, especially neutropenia.Many patients with advanced breast cancer require radiotherapy (RT), which can also cause hematologic toxicity. This study evaluates the impact of combining CDK4/6i with RT on myelosuppression and secondarily on disease-free survival (DFS) and overall survival (OS). Methods: We retrospectively analyzed 73 patients with HR+ HER2- breast cancer treated at Medipol University Faculty of Medicine, Department of Medical Oncology between 2016-2024 using CDK4/6i as first-line treatment. Patients were grouped as no RT (31.5%), concurrent RT (36.9%), or sequential RT (31.5%). Results: While grade 3-4 initial leukopenia was never seen in the non-RT group, grade 3-4 initial leukopenia was seen in 26% of patients who received RT, whether concurrent or sequential (p = 0.023). Similarly, when the deepest grade of leukopenia was evaluated, grade 3-4 leukopenia developed at a higher incidence in the group receiving radiotherapy. Deepest grade 3-4 leukopenia was 64% in the concurrent RT group, 60% in the sequential RT group, and 11.76% in the non-RT group. (p = 0.002) Although there was no difference in neutropenia between the groups, 58% of patients in the general patient population developed grade 3-4 neutropenia. Anemia and thrombocytopenia did not differ between groups. The groups were compared in terms of the frequency of febrile neutropenia that may develop secondary to cytopenia caused by the concomitant use of CDK4/6i and radiotherapy, and no statistically significant difference was observed even though febrile neutropenia was numerically higher in the radiotherapy group. When evaluating disease-free survival, the median DFS was 19.05 months in the group that did not receive RT, 26.53 months in the group that received concurrent RT, and 26.17 months sequentially. We observed a positive effect of RT on overall survival. While OS was 41.75 months in the group without RT, it was 76.9 months in the group with concurrent RT and 75.5 months in the group with sequential RT (p = 0.041). Conclusions: In conclusion, our study shows that administration concurrent or sequential RT and CDK4/6 inhibitors together prolonged disease-free survival and overall survival, but also increased hematologic toxicities. Since these toxicities are manageable, we frequently use RT with CDK4/6i in our clinical practice.