De Novo HER2 S310Y mutation associates with poor response to EGFR tyrosine kinase inhibitor in activating EGFR-mutant NSCLC patient: A case report

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are highly effective in treating lung cancer patients with epidermal growth factor receptor (EGFR)-activating mutations. However, intrinsic resistances of tyrosine kinase inhibitor (TKI) have been reported in 20%–30% of cases. The majority of patients who have primary resistance to EGFR-TKI harbor an insertion in EGFR exon 20 and T790M mutation. Other previously described primary resistance mechanisms include MET amplification, ALK fusion, and KRAS mutation. However, other primary resistance mechanisms have not been fully investigated. Here, we present a 68-year-old Chinese never smoke female with postoperative recurrence of bone and liver metastases after 3 years of surgery, exhibiting combined EGFR and HER2 S310Y mutation by next-generation sequencing panel analysis. The patient responded to gefitinib treatment poorly and showed progressive disease with rapid growth of lung and liver metastasis. This is the first report of activated EGFR mutation patient with a HER2 S310Y mutation had progressed on EGFR-TKI. We suggest that HER2 S310Y mutation probably leads to EGFR-TKI primary resistance in EGFR-mutated NSCLC.