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Dr McArthur on the Expanding Clinical Impact of ADCs in HER2+ Breast Cancer

Supplements and Featured Publications, Dissecting Emerging Data in Metastatic Breast Cancer, Volume 1, Issue 1

Heather McArthur, MD, MPH, discusses the expanding clinical impact of ADCs in HER2-positive breast cancer.

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"Whenever we see this level of innovation in the metastatic space, we typically move those strategies into the curative-intent space with a view of preventing metastases from happening."

Heather McArthur, MD, MPH, the clinical director of Breast Oncology and the Komen Distinguished Chair in Clinical Breast Cancer Research at UT Southwestern Medical Center, discussed the potential role of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in earlier settings of the treatment paradigm for patients with HER2-positive breast cancer, as well as the expanding clinical impact of antibody-drug conjugates (ADCs) the disease space.

According to McArthur, the clinical benefit demonstrated by T-DXd in the metastatic setting has prompted interest in evaluating this agent in curative-intent strategies, where the goal is to prevent the development of distant metastases. Reflecting on her clinical experience, McArthur highlighted a patient who was treated with T-DXd as part of the phase 2 DESTINY-Breast01 trial (NCT03248492) and maintained no evidence of disease for approximately 7 years. Although the patient ultimately experienced disease recurrence, the extended response duration fuels the rationale for outcomes to continue to improve with T-DXd used earlier in treatment.

This perspective aligns with the broader trend of translating successful metastatic therapies into the early-stage setting, where their efficacy may be further amplified. McArthur noted that T-DXd's incorporation into curative regimens could help improve long-term outcomes for select patients with HER2-positive breast cancer, particularly in those with high-risk clinical or pathologic features.

In addition to HER2-targeted ADCs, McArthur emphasized the growing role of ADCs across a wider spectrum of targets and tumor subtypes. Technological advancements in linker and payload design have enhanced the therapeutic index of ADCs, enabling more efficient delivery of cytotoxic agents with reduced systemic toxicity. Early-phase trials investigating novel ADCs directed against alternative targets such as HER3, LIV-1, and PD-1 have shown promising signals of activity, she said, suggesting that future iterations may further broaden therapeutic options.


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