Finding the Best Sequencing Options for ADCs Across Breast Cancer Subtypes

Paolo Tarantino, MD, PhD, highlighted antibody-drug conjugate (ADC) uses among current clinical trials as well as how clinicians are beginning to think about sequencing them across various breast cancer subtypes.

Tarantino, a clinical research fellow at Dana-Farber Cancer Institute, spoke with CancerNetwork® at the 2025 International Congress on the Future of Breast Cancer® East hosted by Physicians' Education Resource®, LLC, to discuss sequencing options, particularly if patients have experienced cross-resistance.

He highlighted a recent study he conducted utilizing the Flatiron Health database to determine whether fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) showed favorable activity in metastatic breast cancer treatment. Additionally, the study findings showed that if patients were given prior sacituzumab govitecan-hziy (Trodelvy), inferior outcomes were observed with T-DXd.

Transcript:

We’re realizing that having more treatments approved is an important opportunity for our patients, and we do need more treatments because these patients cycle through different lines of therapy. After progression, we want to have options. At the same time, we’re realizing that sequencing these agents can come with some degree of cross-resistance. We conducted a large Flatiron Health study with [1490] patients, and we found that there is cross-resistance between T-DXd and sacituzumab govitecan, with sacituzumab used after T-DXd leading to a PFS [progression-free survival] of about 3 months, whereas traditional chemotherapies can lead up to 4 to 5 months.

In truth, we still don’t have prospective data clarifying the role of sequencing. In the absence of that, I usually tend to do what I call the sandwich strategy, meaning that I try to switch the mechanism of action of my treatment after a TOP1 ADC. After T-DXd, I consider using maybe a taxane or capecitabine before going back to another TOP1 ADC. In truth, moving forward, we need to clarify this. We have several prospective trials looking at this: the phase 2 TRADE DXd randomized trial [NCT06533826], the phase 2 SATEEN trial [NCT06100874], [and a] series of many prospective trials. We will start to see data at the end of this year, probably also next year, which will clarify the role of the sequencing of ADCs.

Reference

Tarantino P, Lee D, Foldi J, et al. Outcomes with trastuzumab deruxtecan by biomarker status, line of treatment and prior receipt of sacituzumab govitecan in a large real-world database of patients with metastatic breast cancer. ESMO Open. 2025;10(7):105330. doi:10.1016/j.esmoop.2025.105330