Sequencing Therapies in the Third-Line and Beyond for Patients With HER2+ Metastatic Breast Cancer

The discussion moves to considering other treatment options after progression on trastuzumab deruxtecan (T-DXd). Bhave asks Spring if she would ever use the tucatinib/trastuzumab/capecitabine (HER2CLIMB) regimen in the second-line setting.

Spring responds that the HER2CLIMB regimen is usually reserved for patients with progressive brain metastases, as it has impressive CNS activity. However, emerging data also shows T-DXd has remarkable CNS penetration. For patients without brain metastases, Spring typically uses T-DXd second-line and saves HER2CLIMB for later lines.

Bhave agrees and outlines her typical sequence as T-DXd second-line, then HER2CLIMB third-line, followed by other later options like tyrosine kinase inhibitors (TKIs) with capecitabine, or considering T-DM1 despite lack of data after T-DXd. She asks Spring about her approach in the third-line and beyond setting.

Spring notes the lack of data to definitively guide sequencing after T-DXd and HER2CLIMB. Factors like pace of disease, sites of metastases, and previous durations of response can help weigh using chemotherapy plus anti-HER2 therapy versus trying T-DM1. For brain metastases, she would consider capecitabine which has CNS activity.

Both agree there are many options like TKIs, chemotherapy/anti-HER2 combinations, and margetuximab but limited data on optimal sequencing, highlighting an unmet need for more evidence in later treatment lines. Ultimately, a personalized approach is required based on each patient's disease characteristics and prior therapies.

This summary was AI-generated and edited for clarity.