HER2 in non-small cell lung cancer comprises two distinct conditions: genomic mutations (e.g., exon 20 insertions) treated with Tyrosine Kinase Inhibitors (TKIs), and protein overexpression detected by IHC, treated with Antibody-Drug Conjugates (ADCs). Confusing them leads to incorrect therapy, as TKIs are ineffective for overexpression alone.
Waiting to test for HER2 overexpression until a patient progresses creates significant delays for biopsies and results. This can force clinicians to start less effective treatments while waiting and risks exhausting scarce tissue samples needed for multiple biomarker tests. Testing upfront streamlines second-line therapy decisions.
The nausea from the ADC trastuzumab deruxtecan can be severe and prolonged, comparable to highly emetogenic agents like cisplatin. Clinicians should proactively use an aggressive anti-emetic regimen, treating it like a platinum-based therapy to maintain patient quality of life and treatment adherence.
Unlike pneumonitis from immune checkpoint inhibitors, which responds quickly to steroids, pneumonitis from ADCs like trastuzumab deruxtecan is less responsive and slower to resolve. This critical difference requires a lower threshold for holding therapy and more cautious management to avoid permanent lung damage.