Antibody-Drug Conjugates Such As Datroway and Trodelvy May Transform TNBC

The oncology community is watching the evolving treatment landscape for patients with metastatic triple-negative breast cancer (TNBC), particularly regarding the use of antibody-drug conjugate (ADC) treatments.

Ahead of her talk on frontline treatment and decision making at the CURE Educated Patient® Breast Cancer Summit, held during the 43^rd annual Miami Breast Cancer Conference, Dr. Hope Rugo sat down for an interview to discuss advancements in the field of ADCs.

Rugo is division chief of breast medical oncology and a professor of medical oncology and therapeutics research at City of HopeComprehensive Cancer Center, and also serves as director of the Women’s Cancers Program for City of Hope’s national network of cancer centers.

Transcript

With the 2026 FDA priority review of Datroway (datopotamab deruxtecan-dlnk) in triple-negative breast cancer and the general continued success of ADCs such as Trodelvy (sacituzumab govitecan) in HER2-positive breast cancer, we’re seeing a move away from traditional heavy chemotherapy. For a newly diagnosed patient with metastatic disease, how do you decide when it is safe and effective to choose a targeted option versus standard chemotherapy in the front line?

We have the bright, new shiny drugs, and we always have to understand the implications for moving these drugs earlier in lines of therapy. Can we take drugs that are better than standard chemotherapy in the later line setting, move them to the earlier line and still improve outcome? A lot of this depends on the biology of the disease, and we've seen that with recent data for thinking about patients who have triple-negative breast cancer. We want to put our best foot forward, and that's really clear from all of the data that we have now, these the antibody-drug conjugates that target Trop2 and carry a topoisomerase inhibitor payload, [Datroway] and [Trodelvy] were have now been shown to be superior to standard chemotherapy in the first line setting For progression free survival, and if you don't have everyone have sequence therapy with effective ADCs, you can also improve overall survival, as was shown in the TROPION-Breast02 trial with [Datroway] in patients who received [Trodelvy], they had access to [Trodelvy] in second-line setting, and although progression-free survival was better, overall survival was similar.

This is fascinating, because it does suggest that we don't yet know whether or not it's better to give the drugs first or second line for patients. Now, I would say that in general, it's better because we can't select out the patients who are going to benefit the most from getting these drugs in the first versus second line setting. With our understanding of biology and our clinical trial designs, we just don't have the capacity to do that. And these cancers are so heterogeneous that my take on this data is that it's always better to put your best foot forward, so that we should use the ADCs in general in the first line setting for patients with metastatic triple-negative breast cancer, and then not forget to use our chemotherapy agents sequentially.

After that, we're also learning about sequencing antibody-drug conjugates as new ADCs emerge with new targets and new payloads, which I think is going to be incredibly important for us in the future.

How do we deal with the toxicity of that approach? I think we have to have shared decision making here. Since we don't know that giving these drugs first versus second is going to improve an individual patient's survival, we have to talk balance, the toxicity, the need to come in for IV therapy versus the potential benefits. But I feel like our experience has been that getting a better response earlier and a response that's more durable and is a better approach, putting your best foot forward first.

Transcript has been edited for clarity and conciseness.

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