Strategic Sequencing and Safety: Expert Insights on Breast Cancer ADCs

The rise of antibody-drug conjugates (ADCs) has transformed the treatment landscape for metastatic breast cancer, offering patients targeted options that were unavailable only a few years ago. However, as the number of approved ADCs grows, so does the complexity of managing them.

At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Paolo Tarantino of the Dana-Farber Cancer Institute emphasized that the successful use of these agents requires both a long-term sequencing strategy and meticulous, drug-specific side effect management.

A marathon, not a rush

With three ADCs now approved for metastatic breast cancer, clinicians are often tempted to use them in immediate succession. However, Tarantino warns that this "rush" may lead to cross-resistance.

Recent prospective data suggest that ADCs may not perform as well when administered one after the other without a break. Tarantino explains that ADCs are more than just targeted therapies; the chemotherapy "payload" they carry is a critical factor in their efficacy. If a tumor progresses on one ADC, it may have developed a resistance to that specific type of chemotherapy. To combat this, Tarantino suggests switching mechanisms of action between ADC treatments.

By utilizing traditional therapies such as taxanes, eribulin or vinorelbine after an ADC, clinicians can "reset" the treatment environment. This strategic pause allows for the successful use of a different ADC later in the patient’s journey. Tarantino describes this approach as a marathon, emphasizing that the goal is to sustain effective treatment over the longest possible period.

Precision in prophylaxis

While sequencing is a major focus for the future, the day-to-day safety of these drugs remains a priority for the oncology team. Tarantino noted that although many ADCs are grouped together, their safety profiles are highly distinct. For example, Enhertu (trastuzumab deruxtecan; T-DXd) requires close monitoring for interstitial lung disease (ILD) and cardiotoxicity. Patients on Enhertu should undergo regular CT scans and echocardiograms to ensure their safety.

In contrast, other agents like Datroway (datopotamab deruxtecan; Dato-DXd) present different challenges, such as stomatitis and ocular toxicities. Tarantino highlighted that these side effects require specific prophylactic measures, such as the use of medicated mouthwash and eye drops, which are not typically required for other ADCs.

Furthermore, the management of Trodelvy (sacituzumab govitecan; SG) shifts the focus toward hematologic health. For patients receiving Trodelvy, the primary concern is often neutropenia, which necessitates the proactive use of growth factors to maintain the treatment schedule and prevent infection.

Informing the patient conversation

Tarantino noted that the strategy for using these drugs is constantly evolving as new data from retrospective and prospective studies emerge. These findings are not just for researchers; they are vital tools for the discussions happening between doctors and patients in the clinic

.By understanding the unique nuances of each ADC, from how they are sequenced to how their side effects are prevented, oncologists can ensure that patients remain on therapy longer.

As Tarantino concluded, the right prophylaxis and a strategic "marathon" mindset are the keys to helping patients live longer, healthier lives while managing metastatic disease.

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