Advancements in Treatment Selection and Sequencing in HER2-Positive Metastatic Breast Cancer: Insights from ASCO 2025

Heather McArthur, MD; Laura Huppert, MD; Ruta Rao, MD; William J. Gradishar, MD, FACP; and VK Gadi, MD, PhD, discuss how recent ASCO 2025 data from DESTINY-Breast09 and other studies are reshaping first-line treatment decisions for HER2-positive metastatic breast cancer, with experts debating optimal sequencing strategies between trastuzumab deruxtecan (T-DXd), the CLEOPATRA regimen, and CDK4/6 inhibitor combinations while considering patient-specific factors like central nervous system metastases, hormone receptor status, and quality of life preferences.

EP. 1: Evolving First-Line Treatment Strategies in HER2+ Metastatic Breast Cancer

June 17th 2025

Panelists discuss how the CLEOPATRA regimen (docetaxel, trastuzumab, and pertuzumab) remains the current standard first-line treatment for HER2-positive metastatic breast cancer, with most practitioners using an induction approach followed by maintenance therapy.

EP. 2: Insights from the PATINA Trial: The Role for CDK4/6-Based Maintenance Therapy in HER2+ mBC

June 17th 2025

Panelists discuss how the PATINA trial data showing improved progression-free survival with CDK4/6 inhibitor maintenance therapy after CLEOPATRA induction is becoming practice-changing for patients with hormone receptor–positive disease.

EP. 3: Real-World Insights: Maintenance Strategies and Toxicity Management in HER2+ mBC

June 24th 2025

Panelists discuss how most patients successfully complete induction therapy and transition to maintenance, with best response typically defined by imaging stability after initial tumor shrinkage.

EP. 4: DESTINY-Breast09: Could T-DXd ± Pertuzumab Redefine First-Line HER2+ mBC Treatment?

June 24th 2025

Panelists discuss how the DESTINY-Breast09 trial results showing significant progression-free survival benefit with trastuzumab deruxtecan plus pertuzumab versus standard therapy may shift first-line treatment standards for specific patient populations.

EP. 5: Personalizing First-Line HER2+ mBC Treatment: Balancing Tolerability, Convenience, and Patient Goals in HER2+ mBC

July 1st 2025

Panelists discuss how patient goals, preferences, and the potential for maintenance strategies influence treatment decisions, particularly regarding the continuous versus induction-maintenance approaches with trastuzumab deruxtecan.

EP. 6: DESTINY-Breast09 Deep Dive: CNS Disease, Hormone Receptors, and Treatment Optimization

July 1st 2025

Panelists discuss how patient selection for trastuzumab deruxtecan–based first-line therapy should consider factors like hormone receptor status, disease burden, brain metastases, and the balance between efficacy and quality of life.

EP. 7: The Shifting Paradigm in Second-Line HER2+ mBC Therapy

July 8th 2025

Panelists discuss how evolving first-line options are reshaping second-line and beyond treatment algorithms, with trastuzumab deruxtecan currently preferred in second line and HER2CLIMB regimen in third line regardless of central nervous system metastases status.

EP. 8: Evidence-Based Treatment Selection in Later-Line HER2+ Metastatic Breast Cancer: DESTINY-Breast12 Data and Tucatinib's Evolving Role

July 8th 2025

Panelists discuss how trastuzumab deruxtecan has demonstrated significant central nervous system activity in DESTINY-Breast12, making it an effective option before HER2CLIMB-based regimens, even in patients without existing brain metastases.

EP. 9: Post-THP Strategies: HER2CLIMB-02 Data and Brain Metastases Management

July 15th 2025

Panelists discuss how HER2CLIMB-02 data showing benefit of tucatinib plus T-DM1 provides another treatment option, though its positioning in the evolving treatment landscape remains uncertain given other available regimens.

EP. 10: Strategic Sequencing and Treatment Tailoring in Later-Line HER2+ mBC: Combination vs Monotherapy, CNS Considerations, and Sequencing

July 15th 2025

Panelists discuss how central nervous system (CNS) metastases management is evolving with increased baseline screening considerations and the need to balance radiation timing with antibody-drug conjugate administration to minimize potential toxicity interactions.

EP. 11: Next-Generation Strategies in HER2+ mBC: Sequencing Innovations and Clinical Outlooks

July 22nd 2025

Panelists discuss how the future of HER2-positive treatment will involve more nuanced biomarker-driven approaches, including PIK3CA targeting and circulating tumor DNA monitoring, while acknowledging the challenges these advances create for future drug development.