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Opinion|Videos|April 30, 2025

Clinical Insights Into Treatment Approach for Metastatic HER+ mBC Patient Case

Author(s)Erika P. Hamilton, MD, Heather McArthur, MD, MPH, Kelly E. McCann, MD, PhD

Panelists discuss how they approach treatment sequencing for HER2-positive (HER2+) metastatic breast cancer (mBC) after progression on first-line therapy, including considerations for trastuzumab deruxtecan and the impressive results from the PATINA trial adding CDK4/6 inhibitors to maintenance therapy.

Episodes in this series

3 experts are featured in this series.

EP. 1 Clinical Scenario I: 52-year-old Woman With Recurrent Metastatic HER2+ Breast Cancer

3 experts are featured in this series.

EP. 2 Clinical Insights Into Treatment Approach for Metastatic HER+ mBC Patient Case

3 experts are featured in this series.

EP. 3 Expert Perspectives on Navigating Treatment-Related Adverse Events With T-DXd

3 experts are featured in this series.

EP. 4 Managing Brain Metastases in HER2+ Breast Cancer: Second-Line Treatment Decisions

3 experts are featured in this series.

EP. 5 Forty-Seven-Year-Old Woman With Recurrent HER2+ Breast Cancer and Brain Metastases

3 experts are featured in this series.

EP. 6 Clinical Insights on the Next Treatment Approach for Metastatic HER2+ Breast Cancer with Brain Metastasis

3 experts are featured in this series.

EP. 7 Navigating Third-Line Treatment Options in HER2+ Breast Cancer: ADC or TKI

3 experts are featured in this series.

EP. 8 Tucatinib Combinations in HER2+ Breast Cancer: HER2CLIMB-02 and HER2CLIMB-05

3 experts are featured in this series.

EP. 9 Balancing Efficacy and Tolerability: Expert Insights Into Tucatinib Triplet Therapy for HER2+ Breast Cancer

3 experts are featured in this series.

EP. 10 Clinical Insights Into Managing Heavily Pretreated HER2+ Metastatic Breast Cancer

3 experts are featured in this series.

EP. 11 Looking to the Future: Emerging Therapeutic Approaches in HER2+ Breast Cancer

Clinical Brief: Emerging Options for HER2+ mBC

Key Themes:

Efficacy of Second-Line T-DXd: Trastuzumab deruxtecan (T-DXd) is becoming standard in the second-line setting, supported by National Comprehensive Cancer Network guidelines
PATINA Trial Results: Adding palbociclib to trastuzumab/pertuzumab/AI maintenance therapy significantly improved progression-free survival (PFS) (44 vs 29 months) in hormone receptor (HR)+/HER2+ disease
Biological Heterogeneity: Recognition that HR+, HER2+ disease differs biologically from HR-negative (HR–) disease

Key Points for Physicians:

T-DXd is emerging as the preferred second-line therapy for HER2+ mBC
The PATINA trial data demonstrate significant PFS benefit with the addition of CDK4/6 inhibition to maintenance therapy in HR+/HER2+ disease
Insurance coverage for palbociclib in this setting remains challenging until formal guideline inclusion

Notable Insights:

Approximately 50% of triple-positive (ER+/PR+/HER2+) tumors display luminal characteristics, which may influence treatment response
The 15-month improvement in PFS with palbociclib addition in the PATINA trial was described as “shocking in the most wonderful way”
DESTINY-Breast03 data showed impressive efficacy of T-DXd, with 76% of patients still on therapy at 12 months vs 34% with T-DM1

Clinical Significance:

The treatment landscape for HER2+ mBC is rapidly evolving, with emerging data supporting differentiated approaches for HR+ vs HR– disease and promising results for novel combination strategies that may further improve outcomes.

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