Aditya Bardia, MD, MPH, FASCO
For patients with hormone receptor (HR)–positive, HER2‑negative metastatic breast cancer, the approval of datopotamab deruxtecan (Dato‑DXd; Datroway) offers a new therapeutic option with a differentiated safety profile compared with other antibody–drug conjugates (ADCs) in this setting, according to Aditya Bardia, MD, MPH.
In an interview with OncLive®, Bardia discussed the clinical implications of the FDA approval of Dato‑DXd for adult patients with unresectable or metastatic, HR-positive, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease in January 2025, which was supported by findings from the phase 3 TROPION‑Breast01 trial (NCT05104866).1 He also shared perspectives on optimal patient selection, and addressed how this agent may be sequenced alongside other available ADCs for metastatic breast cancer.
“The approval of Dato-DXd being approved [provides] another therapeutic option available for patients with metastatic breast cancer,” Bardia stated. “It has a different adverse effect [AE] profile and does not cause much neutropenia or diarrhea—unlike another TROP2-directed ADC, [sacituzumab govitecan-hziy (Trodelvy)]—but it [is associated with] AEs such as mouth sores and dry eyes. With its differential AE profile, Dato-DXd gives providers the flexibility to choose the right therapy for each patient. [I’m looking forward to] seeing more data [with this agent as they] emerge.”
Bardia is a professor in the Department of Medicine, Division of Hematology/Oncology, as well as the director of Translational Research Integration at the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center.Top of FormBottom of Form
OncLive: What is the overall significance of the FDA approval of Dato-DXd for HR-positive, HER2-negative metastatic breast cancer?
Bardia: On January 17, 2025, the FDA approved Dato-DXd a [TROP2]-directed ADC, for patients with HR-positive, HER2-negative [breast cancer], which also includes HER2-low metastatic breast cancer, who have received prior endocrine therapy and at least 1e line of chemotherapy.
This was based on the [TROPION-Breast01] study, [in which] patients were randomized to receive [Dato-DXd] or chemotherapy of physician’s choice of chemotherapy in the HR-positive [metastatic breast cancer] setting.
The study showed an improvement in progression-free survival, with a median PFS of 6.9 months with [Dato-DXd] vs 4.9 months with standard chemotherapy. This was clinically meaningful and statistically significant. Additional analyses showed a delay in deterioration of quality of life with [Dato-DXd] compared with standard chemotherapy.
If you look at the AE profile overall, the incidence of grade 3/4 AEs was lower with [Dato-DXd] than with standard chemotherapy. The totality of the data supported [Dato-DXd] as a superior option to standard chemotherapy in this setting, and the FDA granted approval to this drug.
What guidance would you offer clinicians in identifying appropriate patients for this treatment?
We have to contextualize the approval of [Dato-DXd] with the current guidelines and the current therapeutic landscape. In the management of HR-positive metastatic breast cancer, we generally use endocrine-based treatments first. After endocrine-based treatments, we move to chemotherapy and ADCs.
For HER2-low metastatic breast cancer, we often use [fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu)]. For patients with HR-positive breast cancer, both HER2-low as well as -zero, another approved ADC is [sacituzumab govitecan]. [Dato-DXd] would be the third ADC [option] in this setting.
A key question for the field is: How do we sequence these drugs? Do we use T-DXd first and then use Dato-DXd? If we’ve used sacituzumab govitecan, can we then use Dato-DXd? Those are still open questions. But in terms of use, this would be [a good fit] for a patient with HR-positive metastatic breast cancer after endocrine-based options.
What level of accessibility do you expect this agent will have in both community and academic settings?
The drug is available to both academic institutions and community settings. It’s given every 3 weeks and is generally well tolerated.
The two most common [AEs] include mouth sores, for which we recommend a steroid mouthwash, and dry eyes, for which eye drops can be helpful. The incidence of pneumonitis is much lower compared with T-DXd, but it’s still something to be aware of.
What other ADCs are in development for this disease setting?
ADCs continue to expand in development. In terms of what I’m excited to see sacituzumab govitecan is being evaluated in triple-negative breast cancer. Sacituzumab govitecan is also being evaluated in earlier lines for patients with HR-positive, [HER2-negative] metastatic breast cancer in the [phase 3] ASCENT-07 study [NCT05840211]. These drugs are being combined with immunotherapy as well, and they’re also being evaluated for patients with localized breast cancer to prevent recurrence. Increasingly, ADCs are replacing chemotherapy.
Reference
FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. FDA. January 17, 2025. Accessed July 30, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast