Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM)

Breast Cancer. 2024 Nov;31(6):1167-1175. doi: 10.1007/s12282-024-01614-1. Epub 2024 Aug 12.

Abstract

We provide updated results (median follow-up duration: 20.4 months) of a retrospective study on the effectiveness of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer with brain metastases (BM) and/or leptomeningeal disease (ROSET-BM). Median progression-free survival (PFS) was 14.6 months. Median overall survival (OS) was not reached (NR); 24-month OS rate was 56.0%. Subgroup analysis showed that median PFS was 13.2 months in patients with analytical active BM, 17.5 months in patients with leptomeningeal carcinomatosis (LMC), and NR in patients with analytical stable BM (24-month PFS rates in patients with analytical active BM, LMC, and analytical stable BM were 32.7%, 25.1%, and 60.8%, respectively). Median OS was 27.0 months in patients with analytical active BM and NR in patients with LMC or analytical stable BM (24-month OS rates in patients with analytical active BM, LMC, and analytical stable BM were 52.0%, 61.6%, and 71.6%, respectively). The most common adverse event leading to discontinuation of T-DXd was interstitial lung disease (ILD; 23.1%); median ILD onset time among patients who discontinued T-DXd treatment due to ILD was 5.3 months. T-DXd has promising effectiveness in heavily pre-treated HER2+ metastatic breast cancer patients with BM and LMC. The incidence and median onset time of ILD were similar to those of Japanese subgroups in previous studies.

Keywords: Brain metastasis; Breast cancer; HER2+; Leptomeningeal; Trastuzumab deruxtecan.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / mortality
  • Brain Neoplasms* / secondary
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Camptothecin* / analogs & derivatives
  • Camptothecin* / therapeutic use
  • Female
  • Humans
  • Immunoconjugates / therapeutic use
  • Meningeal Carcinomatosis / drug therapy
  • Meningeal Carcinomatosis / mortality
  • Meningeal Carcinomatosis / secondary
  • Meningeal Neoplasms / drug therapy
  • Meningeal Neoplasms / mortality
  • Meningeal Neoplasms / secondary
  • Middle Aged
  • Progression-Free Survival
  • Receptor, ErbB-2* / metabolism
  • Retrospective Studies
  • Trastuzumab* / therapeutic use

Substances

  • Trastuzumab
  • Receptor, ErbB-2
  • trastuzumab deruxtecan
  • ERBB2 protein, human
  • Camptothecin
  • Immunoconjugates
  • Antineoplastic Agents, Immunological