FDA Accepts BLA for Dato-Dxd in HR+/HER2– Metastatic Breast Cancer


The biologics license application for datopotamab deruxtecan has been accepted by the FDA for pretreated HR-positive, HER2-negative metastatic breast cancer.

FDA Accepts BLA for Dato-Dxd in HR+/HER2– Metastatic Breast Cancer

FDA Accepts BLA for Dato-Dxd in HR+/HER2– Metastatic Breast Cancer

A biologics license application (BLA) has been accepted by the FDA to seek approval of datopotamab deruxtecan (Dato-DXd) for adult patients with unresectable or metastatic hormone receptor–positive, HER2-negative breast cancer who previously received systemic therapy for unresectable or metastatic disease.1

The BLA is supported by data from the phase 3 TROPION-Breast01 trial (NCT05104866), which demonstrated that patients treated with Dato-DXd (n = 365) experienced a median progression-free survival (PFS) of 6.9 months (95% CI, 5.7-7.4) compared with 4.9 months (95% CI, 4.2-5.5) for those treated with investigator’s choice of chemotherapy (n = 367; HR, 0.63; 95% CI, 0.52-0.76; P < .0001).2

Notably, overall survival (OS) data were not mature at a median follow-up of 9.7 months; however, a trend was observed favoring Dato-DXd (HR, 0.84; 95% CI, 0.62-1.14).

The FDA has assigned a target action date for the first quarter of 2025 under the Prescription Drug User Fee Act.1

“Despite marked progress in the treatment of hormone receptor–positive, HER2-negative breast cancer, most patients with advanced disease develop endocrine resistance and face the prospect of one or several lines of chemotherapy,” Susan Galbraith, executive vice president, Oncology R&D at AstraZeneca, stated in a news release. “If approved, [Dato-DXd] has the potential to provide these patients an efficacious and better tolerated alternative to conventional chemotherapy.”

TROPION-Breast01 was a randomized, open-label, global study that enrolled patients with hormone receptor–positive, HER2-negative breast cancer who received 1 to 2 lines of chemotherapy in the inoperable or metastatic setting. Disease progression on endocrine therapy or unsuitability for endocrine therapy was required, along with an ECOG performance status of 0 or 1.2

Patients were randomly assigned in a 1:1 fashion to receive Dato-DXd at 6 mg/kg on day 1 of every 3-week cycle, or investigator’s choice of chemotherapy. Chemotherapy options consisted of eribulin mesylate on days 1 and 8 of every 3-week cycle; vinorelbine on days 1 and 8 of every 3-week cycle; gemcitabine on days 1 and 8 of every 3-week cycle; or capecitabine (Xeloda) on days 1 through 14 of every 3-week cycle. Treatment in both arms continued until progressive disease, unacceptable toxicity, or other discontinuation criteria were met.

Stratification factors included lines of prior chemotherapy (1 vs 2), geographic locations (United States, Canada, and Europe vs rest of world), and prior treatment with a CDK4/6 inhibitor (yes vs no).

PFS per RECIST v1.1 criteria as assessed by blinded independent central review and OS served as the trial’s dual primary end points. Secondary end points included overall response rate (ORR), investigator-assessed PFS, and safety.

Additional data showed the ORR was 36.4% in the Data-DXd arm vs 22.9% in the chemotherapy arm. The complete response rate was 0.5% and 0%, respectively.

Safety data showed the rates of any-grade treatment-related adverse effects (TRAEs) were 94% for Dato-DXd and 86% for chemotherapy. Grade 3 or higher TRAEs occurred at rates of 21% and 45%, respectively. TRAEs led to dose reductions in 21% of patients in the Dato-DXd arm vs 30% of patients in the chemotherapy arm. TRAEs led to dose interruptions in 12% and 25% of patients, respectively, and TRAEs led to treatment discontinuation in 3% of patients in each arm. A TRAE resulted in 1 patient death in the chemotherapy arm. The rates of serious TRAEs were 6% for Dato-DXd and 9% for chemotherapy.

The most common any-grade TRAEs reported in at least 15% of patients consisted of anemia (11% with Dato-DXd vs 20% with chemotherapy), neutropenia (11% vs 42%), dry eye (22% vs 8%), nausea (51% vs 24%), stomatitis (50% vs 13%), vomiting (20% vs 8%), constipation (18% vs 9%), fatigue (24% vs 18%), and alopecia (36% vs 21%).

“The FDA’s acceptance of the BLA brings us closer to providing patients with previously treated hormone receptor–positive, HER2-negative breast cancer an alternative option to conventional chemotherapy earlier in the metastatic setting,” Ken Takeshita, MD, global head of R&D at Daiichi Sankyo, added in the news release.1 “Following our recently accepted application for advanced nonsquamous non–small cell lung cancer in the United States, along with additional regulatory reviews underway in China, the European Union, Japan and other regions, we are working swiftly to bring [Dato-DXd] as a potential new treatment option to patients around the world.”


  1. Datopotamab deruxtecan biologics license application accepted in the US for patients with previously treated metastatic HR-positive, HER2-negative breast cancer. News release. AstraZeneca. April 2, 2024. Accessed April 2, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/fda-accepts-dato-dxd-bla-for-breast-cancer.html
  2. Bardia A, Jhaveri K, Im SA, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): primary results from the randomised phase III TROPION-Breast01 trial. Ann Oncol. 2023;34(suppl 2):S1264-S1265. doi:10.1016/j.annonc.2023.10.015
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