Skip to main content

Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases.

Publication ,  Journal Article
Kabraji, S; Ni, J; Sammons, S; Li, T; Van Swearingen, AED; Wang, Y; Pereslete, A; Hsu, L; DiPiro, PJ; Lascola, C; Moore, H; Hughes, M ...
Published in: Clin Cancer Res
January 4, 2023

PURPOSE: Brain metastases can occur in up to 50% of patients with metastatic HER2-positive breast cancer. Because patients with active brain metastases were excluded from previous pivotal clinical trials, the central nervous system (CNS) activity of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is not well characterized. EXPERIMENTAL DESIGN: We studied how T-DXd affects growth and overall survival in orthotopic patient-derived xenografts (PDX) of HER2-positive and HER2-low breast cancer brain metastases (BCBM). Separately, we evaluated the effects of T-DXd in a retrospective cohort study of 17 patients with stable or active brain metastases. RESULTS: T-DXd inhibited tumor growth and prolonged survival in orthotopic PDX models of HER2-positive (IHC 3+) and HER2-low (IHC 2+/FISH ratio < 2) BCBMs. T-DXd reduced tumor size and prolonged survival in a T-DM1-resistant HER2-positive BCBM PDX model. In a retrospective multi-institutional cohort study of 17 patients with predominantly HER2-positive BCBMs, the CNS objective response rate (ORR) was 73% (11/15) while extracranial response rate was 45% (5/11). In the subset of patients with untreated or progressive BCBM at baseline, the CNS ORR was 70% (7/10). The median time on treatment with T-DXd was 8.9 (1.3-16.2) months, with 42% (7/17) remaining on treatment at data cutoff. CONCLUSIONS: T-DXd demonstrates evidence of CNS activity in HER2-positive and HER2-low PDX models of BCBM and preliminary evidence of clinical efficacy in a multi-institution case series of patients with BCBM. Prospective clinical trials to further evaluate CNS activity of T-DXd in patients with active brain metastases are warranted. See related commentary by Soffietti and Pellerino, p. 8.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

January 4, 2023

Volume

29

Issue

1

Start / End Page

174 / 182

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Trastuzumab
  • Retrospective Studies
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Prospective Studies
  • Oncology & Carcinogenesis
  • Immunoconjugates
  • Humans
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kabraji, S., Ni, J., Sammons, S., Li, T., Van Swearingen, A. E. D., Wang, Y., … Lin, N. U. (2023). Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases. Clin Cancer Res, 29(1), 174–182. https://doi.org/10.1158/1078-0432.CCR-22-1138
Kabraji, Sheheryar, Jing Ni, Sarah Sammons, Tianyu Li, Amanda E. D. Van Swearingen, Yanzhi Wang, Alyssa Pereslete, et al. “Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases.Clin Cancer Res 29, no. 1 (January 4, 2023): 174–82. https://doi.org/10.1158/1078-0432.CCR-22-1138.
Kabraji S, Ni J, Sammons S, Li T, Van Swearingen AED, Wang Y, et al. Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases. Clin Cancer Res. 2023 Jan 4;29(1):174–82.
Kabraji, Sheheryar, et al. “Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases.Clin Cancer Res, vol. 29, no. 1, Jan. 2023, pp. 174–82. Pubmed, doi:10.1158/1078-0432.CCR-22-1138.
Kabraji S, Ni J, Sammons S, Li T, Van Swearingen AED, Wang Y, Pereslete A, Hsu L, DiPiro PJ, Lascola C, Moore H, Hughes M, Raghavendra AS, Gule-Monroe M, Murthy RK, Winer EP, Anders CK, Zhao JJ, Lin NU. Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases. Clin Cancer Res. 2023 Jan 4;29(1):174–182.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

January 4, 2023

Volume

29

Issue

1

Start / End Page

174 / 182

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Trastuzumab
  • Retrospective Studies
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Prospective Studies
  • Oncology & Carcinogenesis
  • Immunoconjugates
  • Humans
  • Female