Antoinette Tan, MD, MHS, is chief of Breast Medical Oncology and co-director of the Phase I Program at Levine Cancer Institute, Carolinas HealthCare System; chief of Medical Oncology at Carolinas Medical Center-Pineville; and a Clinical Professor in the Department of Medicine at the University of North Carolina

Antoinette Tan, MD, MHS, discusses the safety profiles of ADCs and ADC selection considerations for breast cancer.

Dr Tan on the Management of ADC-Related Toxicities in Breast Cancer

“In general, antibody-drug conjugates have less treatment-related toxicity compared with standard chemotherapy management [for breast cancer]. There does need to be proactive management of toxicities from ADCs to prevent dose-limiting [adverse] effects.”

Antoinette Tan, MD, MHS, chair of the Department of Solid Tumor and Investigational Therapeutics, chief of the Section of Breast Medical Oncology, and director of the Phase I Program at Atrium Health Levine Cancer; and a clinical professor in the Department of Internal Medicine, Wake Forest University School of Medicine, discussed the safety profile of antibody-drug conjugates (ADCs) for the treatment of patients with breast cancer.

Compared with traditional chemotherapy regimens for the treatment of patients with breast cancer, ADCs generally lead to less treatment-related toxicity, Tan began. Still, the management of toxicities from ADCs should remain a priority to prevent dose-limiting adverse effects (AEs), she noted. Additionally, it’s important to consider dose reduction as a generally effective option to help mitigate ADC-related toxicities, she asserted.

In the current breast cancer landscape, Tan also emphasized that there are a plethora of different types of ADCs that have different targets and payloads, which could affect the AEs that patients may experience. Specifically, if 2 ADCs have the same target but different payloads, the ADCs may demonstrate different safety profiles, she explained. For example, treatment with sacituzumab govitecan-hziy (Trodelvy), a TROP2-directed ADC with an SN-38 payload, has a safety profile that comprises mild suppression with some gastrointestinal toxicities, which is commonly diarrhea, she continued. If a patient presents with conditions that may be prone to causing diarrhea, Tan explained that she may consider choosing a different ADC that is the best fit for the patient.

Furthermore, treatment with fam-trasutuzmab deruxtecan-nxki (T-DXd; Enhertu) has a known safety profile that could lead to interstitial lung disease, Tan added. When considering this treatment, she also acknowledges any underlying lung conditions patients may have, which could arise from prior therapies. Overall, considering patients’ conditions before treatment with ADCs is crucial, especially with limited prospective data on the most recently FDA-approved ADCs for breast cancer, Tan concluded.

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Dr Tan on the Clinical Relevance of T-DXd in HER2-Low/Ultralow Metastatic Breast Cancer

“These are interesting data with seeing an improved PFS using an ADC in the first-line setting compared with chemotherapy. But we also need to weigh the adverse effects [associated] with this ADC.”

Antoinette Tan, MD, MHS, chair of the Department of Solid Tumor and Investigational Therapeutics, chief of the Section of Breast Medical Oncology, and director of the Phase I Program at Atrium Health Levine Cancer; and a clinical professor in the Department of Internal Medicine, Wake Forest University School of Medicine, discussed the clinical implications of findings from the DESTINY-Breast06 trial (NCT04494425), which evaluated fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) vs chemotherapy in patients with chemotherapy-naive, HER2-low or -ultralow metastatic breast cancer.

DESTINY-Breast06 trial demonstrated a significant improvement in progression-free survival (PFS) with T-DXd compared with physician’s choice of chemotherapy. In the HER2-low cohort, T-DXd outperformed chemotherapy. A comparable trend was observed in the HER2-ultralow subgroup, where T-DXd also conferred a longer PFS relative to standard chemotherapy regimens.

These findings are noteworthy, as they suggest that the use of an antibody-drug conjugate (ADC) like T-DXd in the first-line setting can result in superior disease control compared with traditional cytotoxic chemotherapy, according to Tan. However, although the efficacy data are compelling, it is crucial to consider the associated toxicity profile of T-DXd, she said. The trial data indicated a higher incidence of grade 3 or higher adverse effects in patients treated with T-DXd compared with those treated with chemotherapy. Additionally, there was an increased risk of interstitial lung disease, an established and potentially serious complication associated with T-DXd, Tan explained.

 for the treatment of adult patients with unresectable or metastatic, hormone receptor (HR)–positive, HER2-low or -ultralow breast cancer, as determined by an FDA-approved test, that has progressed on at least 1 endocrine therapy in the metastatic setting. This regulatory milestone raises important clinical questions regarding patient selection and optimal treatment sequencing following endocrine therapy, Tan emphasized. In clinical practice, there remain patients who may still derive benefit from less intensive options, such as capecitabine—a well-tolerated, orally administered cytotoxic agent frequently used as a bridge between endocrine therapy and intravenous chemotherapy, she noted.

Nonetheless, for patients with HR-positive, HER2-low metastatic breast cancer and a high visceral disease burden or significant symptomatic presentation, the rapid and durable disease control demonstrated by T-DXd in DESTINY-Breast06 makes the ADC an appealing first-line option, she reported. Ultimately, a tailored, patient-specific approach incorporating shared decision-making is essential in determining the appropriateness of T-DXd, particularly in the first-line metastatic setting, Tan concluded.

Antoinette Tan, MD, MHS, discusses the implications of the DESTINY-Breast06 trial of T-DXd vs chemotherapy in HER2-low or -ultralow breast cancer.

Antoinette Tan, MD, MHS

Articles

Dr Tan on the Management of ADC-Related Toxicities in Breast Cancer

Dr Tan on the Clinical Relevance of T-DXd in HER2-Low/Ultralow Metastatic Breast Cancer