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<p>This study evaluated the real-world effectiveness of trastuzumab deruxtecan (T-DXd) in patients with breast cancer brain metastases (BCBM), generating data from populations underrepresented in clinical trials. Patients with BCBM treated with T-DXd across seven U.S. health systems from 2019 to 2023 were retrospectively identified. HER2 status was classified as HER2-positive (IHC 3 + or IHC 2+/FISH+) or HER2-low (IHC 1 + or IHC 2+/FISH–). Overall survival (OS) was the primary outcome and was evaluated using Kaplan-Meier and log-rank methods for unadjusted comparisons followed by multivariable Cox regression. A total of 111 patients were included (HER2-positive, <i>n</i> = 77; HER2-low, <i>n</i> = 34). HER2-low tumors were more often ER-positive than HER2-positive tumors (79.4% vs. 56.6%, respectively). Overall, 46.8%&#xa0;of patients had received ≥ 6 prior systemic therapy lines. In unadjusted analyses, greater prior chemotherapy exposure was associated with shorter OS (median OS not reached for 0 lines, 35.2 months for 1-2 lines, and 22.1 months for ≥ 3 lines). Median OS was longer in HER2-positive than HER2-low disease (35.2 vs. 12.8 months, respectively). In multivariable analysis, receipt of ≥ 3 prior chemotherapy lines was associated with shorter OS (aHR 9.95, 95% CI 1.20-82.53; <i>p</i> = 0.033), although this finding should be interpreted cautiously given the small sample size, wide confidence interval, and pooled analysis across HER2 subgroups. In this real-world cohort of patients with BCBM treated with T-DXd, HER2-positive disease was associated with longer unadjusted survival than HER2-low disease.&#xa0;Greater prior chemotherapy exposure may reflect poorer underlying prognosis and more heavily pretreated disease. </p>

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Survival outcomes with trastuzumab deruxtecan in HER2-positive vs. HER2-low breast cancer patients with brain metastases: a real-world cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月27日

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  • Vivek Podder,
  • Zouina Sarfraz,
  • Tulika Ranjan,
  • Andrea McCracken,
  • Charlie Hurmiz,
  • Lydia Hodgson,
  • Arun Maharaj,
  • Reshma Mahtani,
  • Manmeet S. Ahluwalia

摘要

This study evaluated the real-world effectiveness of trastuzumab deruxtecan (T-DXd) in patients with breast cancer brain metastases (BCBM), generating data from populations underrepresented in clinical trials. Patients with BCBM treated with T-DXd across seven U.S. health systems from 2019 to 2023 were retrospectively identified. HER2 status was classified as HER2-positive (IHC 3 + or IHC 2+/FISH+) or HER2-low (IHC 1 + or IHC 2+/FISH–). Overall survival (OS) was the primary outcome and was evaluated using Kaplan-Meier and log-rank methods for unadjusted comparisons followed by multivariable Cox regression. A total of 111 patients were included (HER2-positive, n = 77; HER2-low, n = 34). HER2-low tumors were more often ER-positive than HER2-positive tumors (79.4% vs. 56.6%, respectively). Overall, 46.8% of patients had received ≥ 6 prior systemic therapy lines. In unadjusted analyses, greater prior chemotherapy exposure was associated with shorter OS (median OS not reached for 0 lines, 35.2 months for 1-2 lines, and 22.1 months for ≥ 3 lines). Median OS was longer in HER2-positive than HER2-low disease (35.2 vs. 12.8 months, respectively). In multivariable analysis, receipt of ≥ 3 prior chemotherapy lines was associated with shorter OS (aHR 9.95, 95% CI 1.20-82.53; p = 0.033), although this finding should be interpreted cautiously given the small sample size, wide confidence interval, and pooled analysis across HER2 subgroups. In this real-world cohort of patients with BCBM treated with T-DXd, HER2-positive disease was associated with longer unadjusted survival than HER2-low disease. Greater prior chemotherapy exposure may reflect poorer underlying prognosis and more heavily pretreated disease.