Navigating the Data: Later-Line Systemic Therapies for HER2+ Metastatic Breast Cancer

Video content above is prompted by the following:

Later-Line Treatment Options

Key Themes:

• Margetuximab
• Modified trastuzumab with improved immune system interaction

• SOPHIA study showed modest progression-free survival (PFS) improvement over chemotherapy with trastuzumab

• May be particularly beneficial for patients with specific HLA phenotypes
• Tyrosine kinase inhibitors (TKIs)
• Neratinib (irreversible TKI) showed improvement over lapatinib (reversible TKI) in NALA study

• Toxicity considerations include diarrhea and high pill burden

• Potential benefit from targeting both the ligand binding domain and active site of the receptor
• Novel approaches
• TULIP study examined ADC with alkylating agent payload

• Showed PFS improvement, but high ocular toxicity led to lack of FDA approval

• Highlights unpredictable toxicity profiles with different ADC mechanisms

Notable Insights:

• Dr Vidal explained: “All of the antibodies work on sort of in the ligand binding dimerization domain of the receptor. It may also be important to shut down the active site of the receptor, which is where the tyrosine kinase inhibitors function.”

Dr McCann observed: “It’s fascinating how many of these ADCs have just a completely unpredictable toxicity profile that is kind of independent of either where the antigen is, and independent of the payload.”