How would you treat a patient with newly diagnosed stage IV NSCLC who has an activating mutation in the ERBB2 extracellular domain and a concurrent classical EGFR mutation?

No high-level evidence/guidelines for such a situation since oncogenic ECD mutation in HER2 itself is quite uncommon (approximately <10% of HER2 mutations [Robichaux et al., PMID 31588020]), and co-occurrence with classical EGFR mutation will be even less common. Will generally treat based on the cl...

HER-2 alteration can develop in patients on TKI therapy for EGFR-mutated lung cancer. In these cases, HER-2 alterations (amplification or less frequently mutations including rather novel Exon 16 skipping) represent resistance mechanisms.

• Hsu et al., PMID 31557536
• Huang and Fu, PMID 26579470

Denovo E...