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Efficacy and safety of brain radiotherapy combined with antibody-drug conjugates in patients with HER2-positive breast cancer brain metastases.

Created on 18 Aug 2026

Authors

Dongxing Shen, Deyou Kong, Longyu Zhu, Zhikun Liu, Jun Zhang

Published in

Frontiers in oncology. Volume 16. Pages 1899301. Epub Aug 03, 2026.

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.

PMID:
42609284
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

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