Dato-Dxd Shows Survival Improvements in HR+/HER2- Breast Cancer


The dual primary end points of overall survival and progression-free survival were encouraging when patients with hormone receptor-positive, HER2-negative breast cancer were treated with datopotamab deruxtecan.

Breast Cancer: © Crystal light - stock.adobe.com

Breast Cancer: © Crystal light - stock.adobe.com

Datopotamab deruxtecan (Dato-DXd; DS-1062a) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs investigator’s choice of chemotherapy in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low, or negative breast cancer who were treated with a prior endocrine-based therapy and at least 1 systemic therapy, according to results from the phase 3 TROPION-Breast01 study (NCT05104866).1

In addition to positive data for the primary PFS end point, a trend in improvement for the dual primary end point of overall survival (OS) was observed among patients treated with datopotamab deruxtecan compared with chemotherapy. At the time of this interim analysis, OS data were not mature. The study will continue to assess OS.

Datopotamab deruxtecan also had an encouraging safety profile which was consistent with what has been previously seen in clinical trials for patients with breast cancer. There were no new safety signals identified and all grade interstitial lung disease rates were low.

“Today’s TROPION-Breast01 news is a significant development for patients with HR-positive, HER2-low or negative metastatic breast cancer whose tumors have become insensitive to endocrine therapy and who currently face poor outcomes. We are encouraged by these positive results,” said Susan Galbraith, executive vice president, oncology research and development, AstraZeneca, in a press release.

The global, randomized, multicenter, open-label, phase 3 TROPION-Breast01 trial is evaluating datopotamab deruxtecan, a specifically engineered TROP2-directed DXd antibody drug conjugate, to determine its safety and efficacy compared with investigator’s choice of single-agent chemotherapy, including either eribulin, capecitabine, vinorelbine, or gemcitabine. Over 700 patients have been enrolled in the study at sites in Asia, Europe, North America, South America, and Africa.

Patients with inoperable or metastatic HR-positive, HER2-low or -negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer will be assessed if they have who previously progressed on or are not suitable for endocrine therapy per investigator assessment.2 Enrollment in the study is open to patients with an ECOG performance status of 0 or 1, adequate organ and bone marrow function, a minimum life expectancy of 12 weeks at screening, and those who have had an adequate treatment washout period before cycle 1, day 1. Patients who have a history of previously treated neoplastic spinal cord compression, or clinically inactive brain metastases, and those who do not require treatment with corticosteroids or anticonvulsants, are eligible for inclusion in the study if they have recovered from the acute toxic effect of radiotherapy. Additionally, patients must have at least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1., have an available FFPE tumor sample, and agree to use contraception during the duration of the study.

In addition to the dual primary end points of PFS and OS, investigators are assessing the secondary end points of objective response rate, duration of response, investigator-assessed PFS, disease control rate, and time to first subsequent therapy.

Data from the TROPION-Breast01 trial are expected to be presented at an upcoming medical meeting and shared with health authorities.

“The positive topline results from TROPION-Breast01 demonstrate the potential for datopotamab deruxtecan to become an important treatment option for patients with HR-positive, HER2-low or HER2-negative breast cancer in the second-line metastatic setting. We look forward to realizing the full potential of this TROP2-directed antibody drug conjugate across breast cancer subtypes through our ongoing phase III program, including two trials in patients with triple-negative breast cancer,” said Ken Takeshita, MD, global head, oncology research and development, Daiichi Sankyo, in a press release.1

In addition to TROPION-Breast01, datopotamab deruxtecan is being evaluated in 2 additional phase 3 trials for the treatment of breast cancer. The first, TROPION-Breast02 (NCT05374512), is evaluating datopotamab deruxtecan in comparison with chemotherapy for the treatment of patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for anti-PDL1 therapy. In TROPION-Breast03 (NCT05629585), datopotamab deruxtecan will be assessed when given with and without durvalumab (Imfinzi) vs investigator’s choice of therapy in patients with stage I-III TNBC with residual disease after neoadjuvant therapy.

  1. Datopotamab deruxtecan demonstrated statistically significant and clinically meaningful progression-free survival benefit in patients with HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 phase III trial. News release. AstraZeneca. September 22, 2023. Accessed September 22, 2023. https://tinyurl.com/yhbpez8m
  2. A phase-3, open-label, randomized study of dato-DXd versus investigator's choice of chemotherapy (ICC) in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy (TROPION-Breast01). ClinicalTrials.gov. Updated July 13, 2023. Accessed September 22, 2023.
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