Research Article: Efficacy and safety of brain radiotherapy combined with antibody-drug conjugates in patients with HER2-positive breast cancer brain metastases
Abstract:
Antibody-drug conjugates (ADCs) have shown promising efficacy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and brain metastases. This study aimed to investigate the efficacy and safety of brain radiotherapy combined with ADCs in patients with HER2-positive breast cancer and brain metastases in routine Chinese clinical practice. We retrospectively analyzed data from 35 patients with HER2-positive breast cancer and brain metastases treated with brain radiotherapy plus trastuzumab deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1) at the Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, between January 2023 and January 2025. Most patients had prior pyrotinib treatment. Intracranial progression-free survival (iPFS), progression-free survival (PFS), overall survival (OS), and treatment safety were analyzed. Median follow-up was 15.7 months (interquartile range [IQR], 8.7–20.8). Median iPFS was 8.4 months (95% confidence interval [CI] 6.9–9.8), median PFS was 7.9 months (95% CI 5.9–10.4), and median OS was 11.8 months (95% CI 8.6–13.8). Intracranial objective response rate (ORR) was 74.3%, and intracranial disease control rate (DCR) was 94.3%. Median iPFS was 7.6 months in the T-DM1 group versus 10.9 months in the T-DXd group (P < 0.001); median PFS was 6.5 months versus 9.7 months (P = 0.021); median OS was 10.4 months versus 12.9 months (P = 0.046). The most common grade ?3 adverse events were decreased appetite (23%), fatigue (11%), leukopenia (11%), and thrombocytopenia (9%). Among adverse events of special interest, radiation necrosis occurred in 9% (3/35), all were grade 1–2 and occurred exclusively in patients receiving concurrent radiotherapy plus T-DM1; interstitial lung disease occurred in 3% (1/35), grade 1, in the T-DXd group. In Chinese clinical practice, brain radiotherapy combined with either T-DXd or T-DM1 showed promising preliminary efficacy and tolerable safety signals in heavily pyrotinib-pretreated HER2-positive breast cancer patients with brain metastases in this retrospective single-center cohort. In this unadjusted retrospective cohort, patients receiving radiotherapy combined with T-DXd exhibited longer univariate survival outcomes compared with those treated with T-DM1. However, these univariate observational results are preliminary and require prospective multicenter validation with multivariate adjustment.
Introduction:
After lung cancer, breast cancer has become the malignant tumor with the highest risk of brain metastasis ( 1 ). Statistically, 30% of patients with breast cancer will eventually develop brain metastases, and approximately 50% of these cases occur in those with the human epidermal growth factor receptor 2 (HER2)-positive subtype ( 2 ). Local radiotherapy or surgery is one of the standard treatments for brain metastases in patients with breast cancer ( 3 ). However, more than 50% of patients still develop local…
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