Efficacy and Safety of Datopotamab Deruxtecan From a Single-Institution Experience in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer After Multiple Prior Therapies Including Antibody-Drug Conjugates.
- 1Department of Breast Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.
- 2Department of Pharmacy, Saitama Medical University Saitama International Medical Center, Hidaka, Saitama, Japan.
- 3Department of Breast Oncology, Saitama Medical University Hospital, Moroyama-machi, Iruma-gun, Saitama, Japan.
Abstract
Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) with a topoisomerase I inhibitor payload and was approved by the Japan Pharmaceuticals and Medical Devices Agency in 2025 for patients with unresectable or recurrent hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer previously treated with chemotherapy. In the pivotal TROPION-Breast01 trial, most patients had received 1 or 2 prior systemic regimens. However, in routine clinical practice, Dato-DXd is often used in heavily pretreated patients, including those with prior ADC exposure. We evaluated the efficacy and safety of Dato-DXd in this population. We retrospectively analyzed 18 patients with HR+/HER2- metastatic or recurrent breast cancer who received Dato-DXd at our institution between May and December 2025. Clinical data from electronic medical records were reviewed to assess treatment efficacy and treatment-related adverse events (TRAEs). All patients were female, with a median age of 56 years (range, 48-81). Patients were heavily pretreated, with a median of seven prior systemic treatment lines (range, 2-11); 72.2% had previously received trastuzumab deruxtecan (T-DXd). Median real-world progression-free survival (rwPFS) was 3.2 months. Patients with prior T-DXd exposure had significantly shorter rwPFS than T-DXd-naïve patients (2.8 vs. 6.4 months, p < 0.01). TRAEs were generally mild and manageable. The most common TRAEs included alopecia, fatigue, constipation, stomatitis, nausea, and elevated liver transaminases. Five patients required dose reductions, but no treatment discontinuations or fatal events occurred. No cases of interstitial lung disease occurred. In this cohort of heavily pretreated HR+/HER2- metastatic or recurrent breast cancer, Dato-DXd showed limited clinical activity compared with clinical trials, particularly among patients previously treated with T-DXd. Nevertheless, Dato-DXd was safely administered with toxicity management. Further real-world studies are needed to optimize patient selection and treatment sequencing.
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BibTeX
@article{shimada2026efficacy,
title = {{Efficacy and Safety of Datopotamab Deruxtecan From a Single-Institution Experience in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer After Multiple Prior Therapies Including Antibody-Drug Conjugates.}},
author = {Hiroko Shimada and Maki Todo and Hiroshi Ishiguro and Emi Mikami and Wakako Inohana and Taeko Kurosawa and Ayako Nakame and Ayaka Sakakibara and Yuki Ichinose and Akihiro Fujimoto and Asami Nukui and Aya Asano and Hideki Yokogawa and Masahiro Ohara and Kazuo Matsuura and Takahiro Hasebe and Nobuko Fujiuchi and Akihiko Osaki and Toshiaki Saeki},
journal = {Cancer medicine},
year = {2026},
month = nov,
doi = {10.1002/cam4.72457},
url = {https://europepmc.org/article/MED/42998029},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Efficacy and Safety of Datopotamab Deruxtecan From a Single-Institution Experience in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer After Multiple Prior Therapies Including Antibody-Drug Conjugates.
AU - Hiroko Shimada
AU - Maki Todo
AU - Hiroshi Ishiguro
AU - Emi Mikami
AU - Wakako Inohana
AU - Taeko Kurosawa
AU - Ayako Nakame
AU - Ayaka Sakakibara
AU - Yuki Ichinose
AU - Akihiro Fujimoto
AU - Asami Nukui
AU - Aya Asano
AU - Hideki Yokogawa
AU - Masahiro Ohara
AU - Kazuo Matsuura
AU - Takahiro Hasebe
AU - Nobuko Fujiuchi
AU - Akihiko Osaki
AU - Toshiaki Saeki
PY - 2026
DA - 2026/11/01
JO - Cancer medicine
DO - 10.1002/cam4.72457
UR - https://europepmc.org/article/MED/42998029
AB - Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) with a topoisomerase I inhibitor payload and was approved by the Japan Pharmaceuticals and Medical Devices Agency in 2025 for patients with unresectable or recurrent hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer previously treated with chemotherapy. In the pivotal TROPION-Breast01 trial, most patients had received 1 or 2 prior systemic regimens. However, in routine clinical practice, Dato-DXd is often used in heavily pretreated patients, including those with prior ADC exposure. We evaluated the efficacy and safety of Dato-DXd in this population. We retrospectively analyzed 18 patients with HR+/HER2- metastatic or recurrent breast cancer who received Dato-DXd at our institution between May and December 2025. Clinical data from electronic medical records were reviewed to assess treatment efficacy and treatment-related adverse events (TRAEs). All patients were female, with a median age of 56 years (range, 48-81). Patients were heavily pretreated, with a median of seven prior systemic treatment lines (range, 2-11); 72.2% had previously received trastuzumab deruxtecan (T-DXd). Median real-world progression-free survival (rwPFS) was 3.2 months. Patients with prior T-DXd exposure had significantly shorter rwPFS than T-DXd-naïve patients (2.8 vs. 6.4 months, p < 0.01). TRAEs were generally mild and manageable. The most common TRAEs included alopecia, fatigue, constipation, stomatitis, nausea, and elevated liver transaminases. Five patients required dose reductions, but no treatment discontinuations or fatal events occurred. No cases of interstitial lung disease occurred. In this cohort of heavily pretreated HR+/HER2- metastatic or recurrent breast cancer, Dato-DXd showed limited clinical activity compared with clinical trials, particularly among patients previously treated with T-DXd. Nevertheless, Dato-DXd was safely administered with toxicity management. Further real-world studies are needed to optimize patient selection and treatment sequencing.
SN - 2045-7634
ER -