Dato-Dxd Significantly Improves PFS in HR+/HER2-Low or HER2– Breast Cancer


The primary end point of progression-free survival was met in TROPION-Breast01, a phase 3 study of datopotamab deruxtecan for patients with hormone receptor-positive/HER2-negative breast cancer.

Aditya Bardia on Dato-Dxd

Aditya Bardia on Dato-Dxd

Treatment with datopotamab deruxtecan (Dato-Dxd; DS-1062a) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) vs standard of care chemotherapy when used as treatment for patients with inoperable or metastatic hormone receptor-positive/HER2-negative breast cancer, according to results of the TROPION-Breast01 study (NCT05104866).1

Findings were presented at the European Society for Medical Oncology (ESMO) 2023 Congress in Madrid, Spain, and showed that among those given Dato-Dxd, the median PFS was 6.9 months vs 4.9 months for chemotherapy (HR 0.63; 95% CI, 0.52-0.76). Looking at the confirmed overall response rate (ORR), patients treated with Dato-Dxd had an ORR of 36.4% vs 22.9% with chemotherapy.

For the study’s dual primary end point of overall survival (OS), results favored Dato-Dxd over chemotherapy (HR, 0.84; 95% CI, 0.62-1.14) at the interim analysis. However, these results did not reach statistical significance at the time of this data cut-off.

“The study met its primary end point. There was significant improvement in progression-free survival with Dato-Dxd vs standard chemotherapy with a hazard ratio of .63, so that's a 37% reduced risk of disease progression or death,” Aditya Bardia, MD, MPH, director of breast cancer research at Massachusetts General Hospital, told Targeted OncologyTM.


Dato-Dxd is an investigational, specifically engineered TROP2-directed antibody drug conjugate that has a stable linker and is tumor selective.

“Patients with endocrine-resistant metastatic breast cancer generally receive chemotherapy, which is widely used, but chemotherapy can be associated with short progression-free survival, low response rates, as well as significant toxicities like neuropathy and myelosuppression. Clinically, there's a need for better agents,” Bardia explained.

Breast Cancer: © SciePro - stock.adobe.com

Breast Cancer: © SciePro - stock.adobe.com

In this phase 3 TROPION-Breast01 study, over 700 patients at sites in Asia, Europe, North America, South America, and Africa were enrolled and randomized in a 1:1 fashion to receive either Dato-Dxd (n = 365) or investigator’s choice of chemotherapy (n = 367). The study included patients who were previously treated with 1 to 2 lines of chemotherapy, had disease progression on endocrine therapy, or were ineligible for endocrine therapy.2

Investigators evaluated the dual primary end points of PFS and OS. Key secondary endpoints include ORR, duration of response, investigator-assessed PFS, disease control rate, and time to first subsequent therapy.

Patients continued treatment until disease progression, unacceptable toxicity, or other protocol defined criteria.

Additional Data

At ESMO, Bardia presented an efficacy analysis in the intention-to-treat population with a PFS analysis and an interim OS analysis with a median follow-up of 10.8 months.2 Baseline characteristics were well-balanced between the arms. More than 90% of patients had received prior anthracycline or taxanes, and more than 80% had received a prior CDK4/6 inhibitor.

Some patients treated with Dato-Dxd had complete response, while no complete responses were seen with chemotherapy. Additionally, the OS data are currently not mature. However, a trend favoring Dato-Dxd was observed, and more OS results will be presented once the data have matured.

All groups derived benefit regardless of age, race, ECOG performance status, number of prior lines of therapy, and prior use of CDK4/6 inhibitors or taxane and/or anthracycline.

“In terms of response rate, the response rate was also much higher with Dato-Dxd compared with standard chemotherapy. Finally, the overall survival trend was in favor of better Dato-Dxd. The follow-up is ongoing to look at final overall survival results,” added Bardia.

Looking at safety, patients treated with Dato-Dxd had a lower rate of grade ≥ 3 treatment-related adverse events (TRAEs) at 21% vs 45% for those treated with chemotherapy. The rate of treatment interruption was also lower among patients given Dato-Dxd vs chemotherapy.

“The safety profile of Dato-Dxd appeared to be better than standard chemotherapy. The rate of grade 3 or higher AEs were about half with Dato-Dxd compared with standard chemotherapy, and lower risk of treatment discontinuation and interruptions were seen with Dato-Dxd given every 3 weeks, as opposed to chemotherapy agents, which were given day 1 and day 8 every 21 days. All of these factors are important as we consider therapeutic options, not just efficacy, but the safety profile and convenience as well,” said Bardia.

Next Steps

The agent is being evaluated in a comprehensive development programme called TROPION. More than 12 trials are evaluating the efficacy and safety of datopotamab deruxtecan across multiple tumors, including non–small cell lung cancer, triple-negative breast cancer (TNBC), and hormone receptor-positive/HER2-low or negative breast cancer.

In addition to this study, 2 phase 3 trials are evaluating Dato-Dxd in patients with TNBC. The TROPION-Breast02 is a phase 3 study evaluating Dato-Dxd vs chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic TNBC who are not candidates for anti-PD1/PD-L1 therapy. TROPION-Breast03 is another phase 3 study comparing treatment with Dato-Dxd with or without durvalumab (Imfinzi) withto investigator’s choice of therapy in patients with stage I-III TNBC with residual disease after neoadjuvant therapy.

In terms of next steps, Dato-Dxd is moving to early breast cancer and is being evaluated alone or in combination with immunotherapy for patients with triple-negative breast cancer. The next step in terms of research would be building on the study results, and also looking at biomarkers to further refine the study population,” added Bardia.

  1. Datopotamab deruxtecan significantly extended progression-free survival vs. chemotherapy in patients with HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 phase III trial. News release. AstraZeneca. October 23, 2023. Accessed October 24, 2023. https://tinyurl.com/bd658nse
  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 October 11, 2023. Accessed October 25, 2023. https://clinicaltrials.gov/study/NCT05104866
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