Sequencing ADCs in Breast Cancer: Key Clinical Decision Markers

The rapid evolution of antibody-drug conjugates (ADCs) is reshaping oncology, but optimizing their sequencing and timing remains a complex clinical puzzle. At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting,Paolo Tarantino, MD, PhD, an advanced fellow at Dana-Farber Cancer Institute and an editorial advisory board member for the journal ONCOLOGY, discussed the specific clinical markers that guide his treatment choices when transitioning patients between therapies.

From evaluating clinical aggressiveness in hormone receptor (HR)–positive disease to analyzing the precise reasons for progression on a first-line ADC, Tarantino shared how tailored sequencing strategies—reminiscent of traditional chemotherapy management—are paving the way for more personalized breast cancer care.

Transcript:

First of all, there are some settings where you may need to decide to use an ADC or standard chemotherapy, and we’re seeing more and more that ADCs are more efficacious, but they’re not always safer. In some settings, you may want to prefer the ADC if the disease appears more aggressive, clinically. For instance, in patients with ER-positive disease, you start with fam-trastuzumab deruxtecan-nxki [T-DXd; Enhertu] as early as possible if the disease shows aggressiveness after endocrine therapy. But if the disease is indolent instead, you can use capecitabine [Xeloda], for instance. Clinical aggressiveness of the disease is one of the features.

Then, there are the cases where the patient has already received an ADC, and you have to decide if to sequence another ADC. In that case, one interesting predictor that is emerging is the reason for progression on the first ADC. If there was progression, a growth of disease during treatment with the prior ADC, you may want to first utilize something different that works with a different mechanism of action, but many times, there has been a patient [who] has stopped the ADC for toxicity. In that case, using another TOP1 ADC may work because the tumor is still sensitive. [Alternatively], there may be a patient who has received a TOP1 ADC, then stopped for maintenance therapy. Now, we see [that] often in HER2-positive disease, and then there is progression. In that case, reinducing the disease with the ADC could work. We are exploring novel ways of using ADCs, and we will keep on doing that more [often], just like we did with chemotherapy in the past few decades.