Clinical benefit of post-trastuzumab deruxtecan treatment in patients with HER 2-positive unresectable or metastatic breast cancer: A single-institution retrospective observational study

Breast Cancer Res Treat. 2024 Sep;207(2):253-261. doi: 10.1007/s10549-024-07367-x. Epub 2024 May 26.

Abstract

Purpose: Trastuzumab deruxtecan (T-DXd) can improve the prognosis of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, data on treatment recommendations after T-DXd are lacking. Thus, this study aimed to evaluate the treatment options after T-DXd and their effectiveness.

Methods: Patients with HER2-positive MBC were included in this study. Data from clinical records were retrospectively analyzed. The primary outcome was time to treatment failure (TTF). Secondary endpoints were TTF of each treatment and first-line treatment after interstitial lung disease (ILD) and overall survival (OS).

Results: A total of 29 patients were included. Among them, 18 (62%) were hormone receptor-positive. All patients had a median TTF (mTTF) of 3.5 months (95% confidence interval (CI) 2.1-10.03). The mTTF of each treatment, including HER2 tyrosine kinase inhibitor (HER2 TKI), other anti-HER2 treatments, and other treatments, was 2.6, 8.8, and 3.8 months, respectively. No significant differences were observed between treatments, but regimens that include trastuzumab showed a longer TTF than TKI. However, the mTTF among patients who developed T-DXd-related ILD was 2.33 months (95% CI 0.7-not reached), which was shorter than that among those who did not develop ILD (3.83 months, 95% CI 2.1-10.03, hazard ratio: 2.046, 95% CI 0.760-5.507, p = 0.258). The median OS was 14.9 months (95% CI 11.07-29.17).

Conclusion: Treatments after T-DXd showed a shorter mTTF. Regimens that include trastuzumab may be more effective post-T-DXd treatment than HER2 TKI. Further data are needed to establish the best sequential treatment after T-DXd.

Keywords: HER2-positive; Metastatic breast cancer; Post treatment; Time to treatment failure/TTF; Trastuzumab deruxtecan/ T-DXd.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Female
  • Humans
  • Immunoconjugates / therapeutic use
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Receptor, ErbB-2* / metabolism
  • Retrospective Studies
  • Trastuzumab* / therapeutic use
  • Treatment Outcome

Substances

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