Dr Gallagher on Unmet Needs With ADCs in Breast Cancer

Christopher M. Gallagher, MD, medical director, Cancer Services, Washington Cancer Institute, teaching attending physician, MedStar Washington Hospital Center, discusses unmet needs surrounding the use of antibody-drug conjugates (ADCs), as well as questions remaining with other approved agents in breast cancer.

The treatment armamentarium of breast cancer therapeutics continues to advance, presenting opportunities for greater benefit with novel strategies and challenges when harnessing current agents, Gallagher begins. Although ADCs demonstrate heightened efficacy compared with standard chemotherapy, managing patients’ associated toxicities remains a critical unmet need, Gallagher states. Identifying biomarkers for predicting toxicity, particularly in individuals whose disease characteristics disqualify them as candidates for treatment with certain drugs, is also an ongoing challenge, Gallagher adds.

With the continued emergence of ADCs in the breast cancer treatment space, the sequencing of approved agents has become increasingly uncertain, Gallagher continues. Agents like datopotamab deruxtecan (Dato-DXd; DS-1062a) and sacituzumab govitecan-hziy (Trodelvy), the latter of which is currently under investigation in combination with immunotherapy, have demonstrated promising efficacy in patients with breast cancer, he says. However, the incorporation of such regimens into the current armamentarium may further confound treatment selection, Gallagher speculates.

Clinicians often select a therapeutic approach for patient with metastatic breast cancer directly based on the latest research, Gallagher explains. However, ongoing trials assessing post-neoadjuvant therapy and different neoadjuvant therapies may use these agents at earlier stages on metastatic disease management, complicating decision-making, he emphasizes.

Addressing these challenges requires a comprehensive understanding of treatment outcomes, emphasizing the need to clarity sequencing decisions based on evolving therapeutic paradigms, Gallagher states. Oncologists anticipate that results from ongoing trials could better elucidate breast cancer treatment strategies and enhance therapeutic decision-making, Gallagher concludes.

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Christopher M. Gallagher, MD, discusses unmet needs surrounding the use of antibody-drug conjugates, as well as questions remaining with other approved agents in breast cancer.

Dr Gallagher on the Emergence of HER2-Low Metastatic Breast Cancer

Christopher M. Gallagher, MD, medical director, Cancer Services, Washington Cancer Institute, teaching attending physician, MedStar Washington Hospital Center, discusses treatment sequencing considerations with antibody-drug conjugates (ADCs) in patients with HER2-low metastatic breast cancer.

Oncologists should be aware of the potential presence of HER2-low disease when treating patients with metastatic breast cancer, Gallagher says. Prior to the readout of research such as the phase 3 DESTINY-Breast04 trial (NCT03734029), HER2-low was not considered a category of breast cancer, Gallagher notes. Instead, breast cancer with HER2 expression of 1+ or 2+ by immunohistochemistry was defined as hormone receptor (HR)–positive/HER2-negative or triple-negative disease, Gallagher explains. However, HER2-low disease can be either HR-positive or HR-negative, according to Gallagher.

DESTINY-Breast04 evaluated fam-trastuzumab deruxtecan-nxki (Enhertu) vs physician’s choice of chemotherapy in patients with HER2-low metastatic breast cancer who had received 1 or 2 prior lines of chemotherapy. In all patients, trastuzumab deruxtecan elicited a median progression-free survival (PFS) of 9.9 months (95% CI, 9.0-11.3) vs 5.1 months (95% CI, 4.2-6.8) with chemotherapy (HR, 0.50; 95% CI, 0.40-0.63).

In the population of patients with HR-positive disease, the median PFS was 10.1 months (95% CI, 9.5-11.5) with trastuzumab deruxtecan vs 5.4 months (95% CI, 4.4-7.1) with chemotherapy (HR, 0.51; 95% CI, 0.40-0.64). In the population of patients with HR-negative disease, the median PFS was 8.5 months (95% CI, 4.3-11.7) with the ADC vs 2.9 months (95% CI, 1.4-5.1) with chemotherapy (HR, 0.46; 95% CI, 0.24-0.89). These data backed the 

 for the treatment of patients with unresectable or metastatic HER2-low breast cancer.

One future challenge of treating patients with HER2-low metastatic breast cancer will be determining the optimal sequence of ADCs in this setting, Gallagher emphasizes. Some ADCs may be more effective in earlier lines of treatment in this patient population, and investigators need to determine the role of treatment sequencing on patient outcomes, Gallagher says. Ongoing studies are evaluating the optimal treatment sequencing with trastuzumab deruxtecan and TROP2-directed ADCs, such as sacituzumab govitecan-hziy (Trodelvy) and datopotamab deruxtecan (Dato-DXd), Gallagher concludes.

Christopher M. Gallagher, MD, discusses treatment sequencing considerations with antibody-drug conjugates in patients with HER2-low metastatic breast cancer.

Christopher M. Gallagher, MD

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Dr Gallagher on Unmet Needs With ADCs in Breast Cancer

Dr Gallagher on the Emergence of HER2-Low Metastatic Breast Cancer