The Growing ADC Landscape in TNBC Brings Questions, Opportunities: Rebecca Dent, MD, MSc

Rebecca Dent, MD, MSc, deputy CEO and senior consultant at the National Cancer Center in Singapore, discussed the antibody-drug conjugate (ADC) landscape in triple-negative breast cancer (TNBC) and knowledge gaps in their use.

At the European Society for Medical Oncology Congress 2025, Dent presented data showing statistically significant and clinically meaningful improvements in dual primary end points in the phase 3 TROPION-Breast02 (NCT05374512) trial: overall survival (OS) and progression-free survival (PFS) with datopotamab deruxtecan (Dato-DXd) compared with investigator's choice chemotherapy in the first line for locally recurrent inoperable or metastatic TNBC. At a median follow-up of 27.5 months, there was a statistically significant improvement of more than 5 months in both median OS and PFS, with an OS HR of 0.79 (95% CI, 0.64-0.98; P = .0291) and a PFS HR of 0.57 (95% CI, 0.47-0.69; P < .0001).

This transcript was lightly edited; captions are auto-generated.

Transcript

How might Dato-DXd compare, mechanistically and clinically, with other ADCs used in TNBC—are there lessons for sequencing or combination strategies?

There are a number of ADCs now available. We know that there are some differences in the drug-to-antibody ratio across the different ones. I think the 3 that are the most sort of close to the clinic are obviously sacituzumab govitecan, which has been out—that's a day 1 and 8 dosing and has the side effects of myelosuppression, diarrhea, and fatigue, and I think it's a great drug. We don't know how much it has in terms of CNS [central nervous system] penetration, which for my patients is really important.

We see [sacituzumab tirumotecan] as well. We don't have phase 3 data in the Caucasian population. I work in Singapore, so I think it's really important to appreciate that there potentially are pharmacogenomic differences, meaning we might see different side effects. We also might see differences in efficacy. So we're really excited to see how that plays out in a larger group of patients. And I think the most important thing is, how will this look in the curative setting? Because if we have compounds that have CNS activity and it's given in the early breast cancer setting, can we actually increase the chance of cure in our patients? And I guess the final thing is, which ADC is best combined with immune checkpoint inhibition, because there is where we might see the most synergy with the least amount of side effects.

What postprogression patterns were observed, and do these suggest any particular second-line choices?

We certainly have collected that data, and a large number of patients in our trial went on to get antibody-drug conjugates and other novel therapies, because, as I mentioned, part of why it's so important to give your best drug first in triple-negative breast cancer is so that you can stabilize their disease, so that they're fit enough to get second-line therapy. I also think it changes the microenvironment, making subsequent therapies more effective. We do have a lot of very new, exciting compounds out there, like bispecifics that are affecting the microenvironment. The data that we have are very early, but we'll be doing a deep dive into understanding what other therapies patients had access to.

Reference

Dent R, Shao Z, Schmid P, et al. First-line (1L) datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: primary results from the randomised, phase III TROPION-Breast02 trial. Presented at: 50th European Society for Medical Oncology Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA21.