2927 - Safety and Efficacy of Concurrent Tyrosine Kinase Inhibitors (TKIs) and Cranial Radiotherapy for HER2-Positive Breast Cancer Brain Metastases: A Retrospective Real-World Study
Presenter(s)
C. Zhang1, S. Yang2, H. Jing1, H. Fang1, S. Qi1, Y. Song1, X. Liu1, Y. Liu1, W. Zhang1, Y. Tang1, N. Lu1, B. Chen1, S. Chen1, G. Sun1, Y. LI1, Y. Zhai3, and S. Wang1; 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, 2Department of Radiation Oncology, Peking University Shenzhen Hospital, Shenzhen, China, 3Department 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
Purpose/Objective(s): Combining anti-HER2 therapy with radiotherapy for HER2-positive breast cancer brain metastases (BCBM) is controversial. We evaluated the efficacy and safety of concurrent tyrosine kinase inhibitors (TKIs) during cranial radiotherapy in a real-world cohort.
Materials/Methods: We retrospectively analyzed 70 patients with HER2-positive BCBM treated with cranial radiotherapy at our institution between November 2013 and February 2025. Thirty-nine patients received concurrent TKIs (Conc-TKI group) and 31 did not (Non-Conc-TKI group). Concurrent therapy was defined as TKI administration overlapping radiotherapy or within five serum half-lives before or after radiotherapy. The primary endpoint was intracranial progression-free survival (iPFS). Survival outcomes were analyzed using Kaplan–Meier and Cox models, cumulative intracranial progression and radiation necrosis were evaluated with competing-risk models.
Results: The median follow-up was 39 months. Thirty-seven patients received SRS/FSRT and 33 received whole-brain radiotherapy (WBRT) ± simultaneous integrated boost (SIB). In the Conc-TKI group, 74% received pyrotinib. Baseline characteristics were largely balanced, though the Conc-TKI group had a shorter interval from diagnosis to brain metastasis (p=0.035), fewer visceral metastases (62% vs. 87%, p=0.017), and more patients with total intracranial tumor volume =17.1 cc (79% vs. 42%, p=0.001). The overall objective response rate (ORR) was 77.1% and was higher in the Conc-TKI group (87.2% vs. 64.5%, p=0.043). However, no significant differences were observed in median iPFS (19 vs. 16 months, p=0.992), progression free survival (13 vs. 12 months, p=0.500), or overall survival (OS) (33 vs. 39 months, p=0.604) between groups. The 1-year cumulative intracranial progression rates were 18% and 27%, respectively (Gray’s p=0.6). Multivariate analysis showed age >52 years as favorable for iPFS (HR=0.41, p=0.003), while maximal lesion diameter >3 cm was unfavorable (HR=2.45, p=0.004). Higher systemic therapy line (HR=1.33, p=0.001) and more brain metastases (HR=1.02, p=0.001) independently predicted poorer OS. Competing-risk analysis confirmed maximal lesion diameter >3 cm and non-WBRT as adverse for intracranial progression. Acute radiation edema occurred in 61.4% of patients (G3: 4%), with no increase from concurrent TKI (66.7% vs. 54.8%, p=0.272). The incidence of radiation necrosis was 18.6%, with no difference between groups (Conc-TKI vs. Non-Conc-TKI: any grade 20.5% vs. 16.1%, p=0.761; symptomatic 10.3% vs. 9.7%, p>0.999). Multivariable competing-risk analysis confirmed equivalent dose in 2-Gy fractions (EQD2) as the sole independent risk factor for radiation necrosis, while TKI exposure did not increase the hazard.
Conclusion: Concurrent TKI therapy with cranial radiotherapy is a safe and effective strategy for HER2-positive BCBM. It significantly enhances the ORR without increasing the risk of radiation necrosis.