Dr O’Meara on the Evolving Role of ADCs in HER2+ Breast Cancer

"There’s been a lot of exciting work about ADCs over the past few years, and every month, there’s been something new. A major theme with T-DXd has been figuring out how low we can go in terms of HER2 expression for which T-DXd is still efficacious.”

Tess O’Meara, MD, a clinical fellow in medicine at the Dana-Farber Cancer Institute, highlighted the evolving role of antibody-drug conjugates (ADCs) in the treatment of patients with HER2-positive breast cancer.

Within the past few years, there has been substantial work done in the ADC space for breast cancer, with new findings seemingly being reported every month, O’Meara began. She noted that a major theme with the continued evaluation of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) has been identifying the efficacy limit of the ADC regarding low HER2 expression. More data are demonstrating that very low HER2 expression suffices to generate good clinical activity with T-DXd, she explained. Furthermore, T-DXd may also have a role in the HER2-null, she added.

Additionally, O’Meara emphasized that studies are evaluating ADCs in earlier lines of treatment beyond the later lines of metastatic breast cancer, including in the first-line setting, and as adjuvant and neoadjuvant treatment. Studies evaluating combinations are also needed, she continued, adding that these trials will be needed to help guide strategies for maintenance, she explained. Specifically, the phase 3 PATINA study (NCT02947685), established that the addition of a CDK4/6 inhibitor and endocrine therapy showed benefit in patients with hormone receptor (HR)–positive, HER2-positive breast cancer, she said. If T-DXd is utilized in the first-line setting, 1 question will be whether it should be combined with other agents or used as a maintenance strategy, O’Meara concluded.

Of note, the PATINA study evaluated the efficacy and safety of palbociclib (Ibrance), plus anti-HER2 therapy consisting of trastuzumab (Herceptin) or pertuzumab (Perjeta), and endocrine therapy for the treatment of patients with HR-positive, HER2-positive metastatic breast cancer.

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