TROPION-Breast01: The Evolving Role of TROP2-Directed ADCs in Breast Cancer

In part 2 of this interview, we continue our discussion with Aditya Bardia, MD, MPH, FASCO, medical oncologist, UCLA Health, on recent findings from the TROPION-Breast01 trial (NCT05104866), presented at an ESMO Virtual Plenary in February 2025.

In this discussion, Bardia covers the need for subgroup analyses, managing adverse events, and ongoing studies involving TROP2-directed antibody drug conjugates (ADCs).

This transcript was lightly edited and captions were auto generated.

Transcript

Were there any notable differences in response based on prior CDK4/6 inhibitor use, or in specific patient subgroups within the trial?

If you look at the subgroups related to TROPION-Breast0— including patients who had prior CDK4/6 inhibitor [use], patients with brain metastases, and other subgroups— in all the subgroups, that of Dato-DXd [datapotamab deruxtecan] was superior to standard chemotherapy, so there's no specific subgroup where the results were inferior. We need more biomarker results, looking at TROP2 [and] looking at other biomarkers to see if there's a subgroup that derived more benefit than the other group.

What strategies do you recommend for managing the adverse events associated with the datapotamab deruxtecan?

Datapotamab deruxtecan overall is generally well-tolerated, as described in the clinical trial. The 2 common side effects include mucositis (usually a steroid mouthwash can at least reduce the severity of mucositis) and the second is keratitis, or dry eye. Rarely, the drug can also cause pneumonitis, but much lower frequency than TD-Xt [trastuzumab deruxtecan] side effects that occur at a very low frequency with that of Dato-DXd, [which] include neutropenia. That's something important to remember as there are multiple ADCs approved in this setting. So, the side effect profile does dictate which ADC to use.

How do you see the role of TROP2-directed ADCs evolving in the landscape of metastatic breast cancer treatment, and are there ongoing studies exploring combination strategies with this agent?

We currently now have 2 TROP2-directed ADCs that are FDA approved, sacituzumab govitecan and now, more recently, datapotamab deruxtecan. These drugs are also being evaluated in the first-line setting, with/without immunotherapy for patients with metastatic TNBC, as well as localized breast cancer. So, these ADCs are slowly replacing chemotherapy, and we are excited about the development of these ADCs.