Navigating Treatment Sequencing in HER2+ Metastatic Breast Cancer: Evidence-Based Approaches

Panelists discuss how a 52-year-old elementary school teacher diagnosed with HER2-positive (HER2+) breast cancer achieved pathologic complete response with neoadjuvant therapy but experienced metastasis 18 months after completing treatment, requiring first-line metastatic therapy.

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.

Panelists discuss how they manage adverse effects of trastuzumab deruxtecan (T-DXd), particularly focusing on nausea, fatigue, and the critical monitoring needed for interstitial lung disease (ILD), with recommendations for prophylactic antiemetics and frequent imaging.

Panelists discuss how the presence of brain metastases influences treatment decisions in HER2-positive (HER2+) breast cancer, highlighting the DESTINY-Breast12 trial demonstrating trastuzumab deruxtecan’s (T-DXd) efficacy in patients with brain metastases.

Panelists discuss how they approach the case of a 47-year-old marketing executive with initially low-risk HER2-positive (HER2+) breast cancer who developed brain, liver, lung, and bone metastases shortly after completing adjuvant therapy.

Panelists discuss how they would approach multiple brain metastases at initial metastatic diagnosis, debating the use of stereotactic radiosurgery vs systemic therapy with agents that cross the blood-brain barrier.

Panelists discuss how National Comprehensive Cancer Network (NCCN) guidelines inform third-line treatment options for HER2-positive (HER2+) metastatic breast cancer, with particular focus on the HER2CLIMB regimen (tucatinib, capecitabine, and trastuzumab) for patients with brain metastases.

Panelists discuss how the HER2CLIMB-02 and HER2CLIMB-05 trials might impact treatment sequencing, with particular interest in using tucatinib earlier in treatment to potentially prevent brain metastases.

Panelists discuss how they manage adverse effects of tucatinib-based therapy, particularly focusing on diarrhea and palmar-plantar erythrodysesthesia from capecitabine, with practical dosing strategies to improve tolerability.

Panelists discuss how they approach treatment beyond third-line therapy for HER2-positive (HER2+) metastatic breast cancer, considering factors such as prior therapies, residual toxicities, and patient preferences when selecting from multiple options.

Panelists discuss how emerging developments in HER2-positive (HER2+) breast cancer treatment, including novel antibody-drug conjugates, bispecific antibodies, and cytotoxic-sparing regimens for hormone receptor+ (HR+)/HER2+ disease, are creating exciting new options for patients.