321 - Phase I/II Study of Concurrent Abemaciclib and Adjuvant Radiotherapy in Patients with HR+, HER2-, High-Risk Breast Cancer
Presenter(s)
Y. Song1, Y. Zhai2, B. Lan3, X. Zhao1, Z. Li1, Z. Qiu1, X. Shen1, C. Zhang1, G. Sun1, S. Chen1, H. Fang1, H. Jing1, Y. Wang4, F. Ma3, and S. Wang5; 1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 2State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 3Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 4Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 5State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
Purpose/Objective(s): This phase I/II dose-escalation trial aimed to evaluate the safety and feasibility of concurrent abemaciclib and locoregional radiotherapy (RT) in patients with hormone receptor–positive (HR+), HER2-negative, high-risk breast cancer
Materials/Methods:
This study was registered at ClinicalTrials.gov and consisted of two parts. In the phase I part, a standard 3+3 dose-escalation design was used to determine the dose-limiting toxicities (DLTs) and establish the maximum tolerated dose (MTD) of abemaciclib when combined with RT. In the phase II component, an expansion cohort was enrolled at the MTD to further evaluate the safety profile and refine DLT assessment in a broader patient population. Abemaciclib was administered at escalating doses of 50 mg, 100 mg, or 150 mg twice daily. All patients received modern RT techniques, including hypofractionated or conventional fractionation, targeting the breast or chest wall with regional nodal irradiation as clinically indicated. Acute and late toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was determination of the MTD of abemaciclib administered concurrently with locoregional RT.Results: Between 2024 and 2025, 40 patients with HR+/HER2- breast cancer receiving concurrent abemaciclib and locoregional RT were enrolled. All patients completed RT as planned. In phase I, 12 patients were enrolled: three received 50 mg twice daily, three received 100 mg twice daily, and six received 150 mg twice daily. Only one patient in the 150 mg twice-daily cohort experienced DLTs (grade 3 leukopenia and grade 3 neutropenia). In phase II, 28 patients were enrolled and received abemaciclib at 150 mg twice daily. Abemaciclib interruption occurred in 12 patients (42.9%), primarily due to grade 3 leukopenia, grade 3 neutropenia, or grade 2–3 thrombocytopenia. Across the entire cohort, the most common hematologic toxicities of any grade were leukopenia (97.5%), lymphopenia (92.5%), and neutropenia (82.5%). The most common non-hematologic toxicities of any grade were radiation dermatitis (100%), diarrhea (40.0%), and fatigue (35.0%). Grade 3 radiation induced dermatitis was observed in 1 patient No grade =2 pneumonitis was observed during RT or within six months post-RT. No grade =4 toxicities were reported.
Conclusion:
The 150 mg twice-daily dose of abemaciclib demonstrated a favorable safety profile during phase I dose escalation. The observed adverse events were consistent with those expected from abemaciclib or radiotherapy alone. Although grade 3 leukopenia and neutropenia were common, these events were manageable, reversible. Importantly, no increase in pneumonitis was observed. These findings provide valuable prospective evidence to inform clinical practice and support further investigation into the efficacy of concurrent radiotherapy and abemaciclib. (NCT06197581)