Dato-DXd in Advanced or Metastatic HR-Positive/HER2-Negative or Triple-Negative Breast Cancer

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In the phase I TROPION-PanTumor01 trial reported in the Journal of Clinical Oncology, Aditya Bardia, MD, PhD, and colleagues found that the antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) was active in patients with locally advanced or metastatic hormone receptor (HR)-positive/HER2-negative and triple-negative breast cancer.

Aditya Bardia, MD, PhD

Aditya Bardia, MD, PhD

Study Details

Eighty-five patients were enrolled in the study at sites in the United States and Japan between June 2020 and October 2021, including 41 with HR-positive/HER2-negative disease and 44 with triple-negative disease. Patients received Dato-DXd at 6 mg/kg (n = 83) or 8 mg/kg (n = 2) every 3 weeks until disease progression or unacceptable toxicity. Patients had received a median of three to five (range = 1–10) prior treatments in the locally advanced/metastatic setting.


Objective responses on blinded independent central review were observed in 11 (26.8%, 95% confidence interval [CI] = 14.2%–42.9%) of 41 patients in the HR-positive/HER2-negative group (all partial) and in 14 (31.8%, 95% CI = 18.6%–47.6%) of 44 in the triple-negative group (complete response in 1). Median response durations were not reached (95% CI = 4.4 months to not reached) and 16.8 months (95% CI = 5.6 months to not reached), respectively. Disease control rates were 85.4% and 79.5%.

Median progression-free survival was 8.3 months (95% CI = 5.5–11.1 months) in the HR-positive/HER2-negative group and 4.4 months (95% CI = 3.0–7.3 months) in the triple-negative group. Median overall survival was not reached and 13.5 months (95% CI = 10.1–16.3 months) in the two groups, respectively.


  • Dato-DXd produced objective response in 26.8% of patients with HR-positive/HER2-negative breast cancer and 31.8% of those with triple-negative disease.
  • Median response durations were not reached and 16.8 months, respectively.

Adverse Events

The most common adverse events of any grade (grade ≥ 3) were stomatitis (82.9%, 9.8%), nausea (56.1%, 0%), and fatigue (46.3%, 2.4%) in the HR-positive/HER2-negative group, and stomatitis (72.7%, 11.4%), nausea (65.9%, 2.3%), and vomiting (38.6%, 4.5%) in the triple-negative group. Grade ≥ 3 adverse events were observed in 41.5% of patients in the HR-positive/HER2-negative group (22.0% determined to be drug-related) and 52.3% of the triple-negative group (25.0% drug-related).

Adverse events led to discontinuation of treatment in 12.2% and 2.3% of patients. One patient in the HR-positive/HER2-negative group died from dyspnea, considered unrelated to treatment.

The investigators concluded, “In patients with heavily pretreated advanced HR-positive/HER2-negative and triple-negative breast cancer, Dato-DXd demonstrated promising clinical activity and a manageable safety profile. Dato-DXd is currently being evaluated in phase III studies.”

Funda Meric-Bernstam, MD, of the Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Daiichi Sankyo, Inc. For full disclosures of the study authors, visit

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