Dato-DXd Secures EU Approval for Pretreated HR+/HER2– Metastatic Breast Cancer

Dato-DXd in HR+/HER2– | Image Credit:

© Sebastian Kaulitzki – stock.adobe.com

The European Commission has approved datopotamab deruxtecan (Dato-DXd; Datroway) for the treatment of adult patients with unresectable or metastatic hormone receptor–positive, HER2-negative (immunohistochemistry [IHC] 0, IHC 1+, or IHC 2+/in situ hybridization–) breast cancer who have received endocrine therapy and at least 1 line of chemotherapy in the advanced setting.1

The regulatory decision was supported by data from the phase 3 TROPION-Breast01 trial (NCT05104866), which showed that patients treated with Dato-DXd (n = 365) achieved a median progression-free survival (PFS) of 6.9 months (95% CI, 5.7-7.4) per blinded independent central review (BICR) compared with 4.9 months (95% CI, 4.2-5.5) for those given investigator’s choice of chemotherapy (n = 367; HR, 0.63; 95% CI, 0.52-0.76; P < .0001).2 Per investigator assessment, the median PFS was 6.9 months vs 4.5 months, respectively (HR, 0.64; 95% CI, 0.53-0.76).

Notably, data from the trial’s final overall survival (OS) analysis showed that Dato-DXd did not significantly improve OS vs chemotherapy.3

“With the majority of breast cancer cases historically considered hormone receptor–positive, HER2-negative, additional treatment options are needed to improve outcomes for patients with metastatic disease that continues to progress following endocrine-based therapy and initial chemotherapy,” Barbara Pistilli, MD, head of the Breast Cancer Unit in the Medical Oncology Department of Gustave Roussy Cancer Center in Villejuif, France, stated in a news release.1 “The approval of Dato-DXd in the European Union [EU] will provide these patients with a new treatment option that can help slow the progression of this disease.”

In January 2025, the FDA approved datopotamab deruxtecan-dlnk for adult patients with unresectable or metastatic, hormone receptor–positive, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.4 This approval was also based on findings from TROPION-Breast01.

TROPION-Breast01 Rundown

The global, randomized, open-label phase 3 study enrolled patients with hormone receptor–positive, HER2-negative breast cancer who received 1 to 2 lines of prior chemotherapy in the inoperable/metastatic setting.2 Disease progression on endocrine therapy was also required, and patients needed to be unsuitable for additional endocrine therapy. An ECOG performance status of 0 or 1 was also necessary for enrollment.

Patients were randomly assigned 1:1 to receive Dato-DXd at 6 mg/kg once every 3 weeks or investigator’s choice of chemotherapy comprising eribulin mesylate, vinorelbine, gemcitabine, or capecitabine.

BICR-assessed PFS per RECIST 1.1 criteria and OS served as the trial’s dual primary end points. Secondary end points included overall response rate, investigator-assessed PFS, and safety.

Additional data presented at the 2023 ESMO Congress showed that patients in the Dato-DXd arm experienced an ORR of 36.4%, including a complete response rate of 0.5%, compared with an ORR of 22.9% for chemotherapy; all responses in the control arm were partial.

Regarding safety, any-grade treatment-related adverse effects (TRAEs) were reported in 94% of patients in the Dato-DXd arm vs 86% of patients in the chemotherapy arm. The rates of grade 3 or higher TRAEs were 21% and 45%, respectively. Any-grade serious TRAEs were reported in 6% of patients in the experimental arm vs 9% of those in the control arm. The respective rates of grade 3 or higher serious TRAEs were 5% and 8%.

TRAEs led to dose reductions, dose interruptions, and treatment discontinuation in 21%, 12%, and 3% of patients, respectively. In the control arm, these respective rates were 30%, 25%, and 3%. TRAEs did not lead to any deaths in the Dato-DXd arm vs 1 death (0.3%) in the chemotherapy arm.

“Treating metastatic hormone receptor–positive, HER2-negative breast cancer presents challenges, particularly treatment resistance and disease progression that occur following endocrine-based therapy and initial chemotherapy,” Ken Keller, global head of Oncology Business, president, and chief executive officer of Daiichi Sankyo, added in a news release.1 “[Dato-DXd] represents the second antibody-drug conjugate approved for breast cancer based on Daiichi Sankyo’s DXd technology and the third medicine to be approved in the EU from our oncology pipeline, underscoring our commitment to creating new medicines for patients with cancer.”

References

1. Datroway approved in the EU for patients with previously treated metastatic HR positive, HER2 negative breast cancer. News release. Daiichi Sankyo. April 8, 2025. Accessed April 8, 2025. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202504/20250408_E2.pdf
2. Bardia A, Jhaveri K, Im S, 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
3. Datopotamab deruxtecan final overall survival results reported in patients with metastatic HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 Phase III trial. News release. AstraZeneca. September 23, 2024. Accessed April 8, 2025. https://www.astrazeneca.com/media-centre/press-releases/2024/datopotamab-deruxtecan-final-overall-survival-results-reported-in-patients-with-metastatic-hr-positive-her2-low-or-negative-breast-cancer-in-tropion-breast01-phase-iii-trial.html#!
4. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. FDA. January 17, 2025. Accessed April 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast