Anne P. O’Dea, MD

Panelists discuss how the continued evolution of HER2-directed therapies, particularly the expanding role of trastuzumab deruxtecan (T-DXd) across different breast cancer settings, has transformed the treatment landscape, while emphasizing the importance of appropriate patient selection, optimal sequencing strategies, and the need for education around early adoption of promising therapies in community practice settings.

Panelists discuss how emerging data from trials such as DESTINY-Breast09, which is evaluating first-line trastuzumab deruxtecan (T-DXd) with or without pertuzumab, could potentially reshape the treatment paradigm for HER2+ metastatic breast cancer (mBC) by establishing new standards for initial therapy and optimal combination approaches.

Panelists discuss how sequential therapy selection for patients with HER2+ breast cancer with progressive brain metastases requires careful consideration of prior treatments, patterns of progression, symptom burden, and available clinical trials, while balancing the need for both systemic disease control and CNS -specific approaches.

Panelists discuss how the DESTINY-Breast12 trial evaluated trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer (mBC) with brain metastases, demonstrating encouraging intracranial responses and overall survival outcomes while maintaining a manageable safety profile consistent with previous T-DXd studies.

Panelists discuss how treatment selection for patients with HER2+ breast cancer with brain metastases requires careful consideration of factors such as metastatic burden, symptomatology, and prior therapies, typically incorporating both local approaches and systemic agents with CNS activity while accounting for individual patient characteristics such as performance status, comorbidities, and preferences in developing personalized treatment plans.

Panelists discuss how patients with HER2+ breast cancer frequently develop brain metastases, with recent pivotal trials such as HER2CLIMB and DESTINY-Breast03 demonstrating improved intracranial responses with newer agents such as tucatinib, and how trastuzumab deruxtecan leads to evolving standards of care (SOC) that now incorporate these targeted therapies alongside traditional local therapies.

Panelists discuss how trastuzumab deruxtecan’s (T-DXd's) key adverse events (AEs) include interstitial lung disease, neutropenia, and nausea/fatigue, emphasizing the importance of proactive monitoring, early intervention through coordinated multidisciplinary care, and comprehensive patient education with clear communication channels for reporting symptoms.

Panelists discuss how trastuzumab deruxtecan (T-DXd) demonstrated favorable patient-reported outcomes and quality of life measures in HER2-low hormone receptor-positive metastatic breast cancer patients in DESTINY-Breast06, suggesting it could be a well-tolerated therapeutic option that maintains patients' daily functioning while providing clinical benefit.

Panelists discuss how emerging data on HER2-ultralow breast cancer is informing treatment decisions, particularly regarding the potential role of trastuzumab deruxtecan, while acknowledging the need for careful patient selection and consideration of traditional treatment sequences.

Panelists discuss how DESTINY-Breast06 demonstrated meaningful clinical activity of trastuzumab deruxtecan in both HER2-low and ultralow metastatic breast cancer populations.

Panelists discuss how clinical trials like DESTINY-Breast04, TROPiCS-02, and TROPION-Breast01 have revolutionized treatment options for HER2-low advanced breast cancer by validating novel targeted therapies and antibody-drug conjugates.

Panelists discuss how evolving HER2 classification methods and recent trial data are reshaping treatment approaches for advanced breast cancer, particularly regarding the clinical significance of HER2-low and ultralow categories.

Closing out their discussion on HR+, HER2- breast cancer, expert panelists share their excitement for further evolution in the treatment paradigm.

Expert perspectives on trial results with both IO and PARP inhibitor therapy, respectively, in the setting of relapsed/refractory HR+/HER2- breast cancer.

A brief discussion on the use of antibody drug conjugates in patients with relapsed/refractory breast cancer and HER2-low expression.

Centering discussion on the TROPICS-02 and DESTINY-Breast04 trials, panelists consider the advent of antibody drug conjugates in relapsed/refractory HR+ breast cancer.

Shared insight on the potential role of CDK4/6 inhibitors in the second-line setting of relapsed/refractory HR+/HER2- breast cancer.

Expert perspectives on the current paradigm of PI3K inhibition in the setting of relapsed/refractory HR+/HER2- breast cancer.

A brief overview of oral SERDs currently being investigated in the setting of relapsed/refractory HR+/HER2- breast cancer.

Panelists briefly consider the ongoing role of everolimus in relapsed/refractory HR+/HER2- breast cancer given recent shifts in the treatment paradigm.

Comprehensive insight on novel treatment approaches in the setting of relapsed/refractory HR+/HER2- breast cancer, including oral SERDs, SERMs, and ER PROTAC degraders.

Shifting their focus to the HR+/HER2+ setting of breast cancer, expert panelists consider the potential of CDK4/6 inhibition in light of clinical trial data.

A brief review of frontline combination strategies in the context of multiple driver pathways in HR+/HER2- breast cancer.

Experts home in on real-world data and resistance mechanisms to discuss practical use of CDK4/6 inhibition in HR+/HER2- breast cancer.v

Comprehensive insight on the barriers to CDK4/6 inhibition in HR+/HER2- breast cancer, from both medical and accessibility perspectives.

Taking into account all 3 available CDK4/6 inhibitors in HR+/HER2- breast cancer, experts consider how they’d select frontline therapy in this setting.

Panelists share insight on clinical trial data behind use of palbociclib in the frontline setting of HR+/HER2- breast cancer.

Focusing on the frontline setting of HR+/HER2- breast cancer, panelists discuss clinical trial data with abemaciclib and ribociclib, respectively.

Expert perspectives on the evolving treatment paradigm for patients receiving frontline therapy for HR+/HER2- breast cancer.

After discussing a few more key datasets from the SABCS 2021 Virtual Meeting, expert panelists discuss how they would approach treatment in several subsets of breast cancer.