Treatment Order for Patients with HER2+ Metastatic Breast Cancer After Second Line of Therapy

After progressing on trastuzumab deruxtecan (T-DXd), the discussion shifts to exploring alternative treatment options. Bhave inquires Spring about the potential use of the tucatinib/trastuzumab/capecitabine (HER2CLIMB) regimen in the second-line setting.

Spring explains that typically, the HER2CLIMB regimen is reserved for patients with progressive brain metastases due to its impressive CNS activity. However, emerging data also indicates that T-DXd has significant CNS penetration. For patients without brain metastases, Spring usually opts for T-DXd as a second-line treatment and reserves HER2CLIMB for later lines.

Bhave concurs and outlines her usual sequence of T-DXd as second-line, followed by HER2CLIMB as third-line, and then considering other options like tyrosine kinase inhibitors (TKIs) with capecitabine, or T-DM1 despite the lack of data post-T-DXd. She asks Spring about her strategy for the third-line and beyond.

Spring emphasizes the scarcity of data to definitively guide sequencing post-T-DXd and HER2CLIMB. Factors such as disease progression rate, metastatic sites, and previous response durations can assist in deciding between chemotherapy plus anti-HER2 therapy or attempting T-DM1. For patients with brain metastases, Spring suggests considering capecitabine due to its CNS activity.

Both experts agree on the numerous options available, including TKIs, chemotherapy/anti-HER2 combinations, and margetuximab. However, there is limited data on the optimal sequencing, underscoring the need for more evidence in later treatment lines. Ultimately, a tailored approach is necessary based on each patient’s specific disease characteristics and prior treatments.