Long-Term Progression-Free Survival With First-Line Pyrotinib Monotherapy in a Treatment-Naïve Stage IV NSCLC Patient Harboring an ERBB2 Exon 20 Insertion: A Case Report

Zhenyu KeHongbo YangMeng XingShashan Bi^*Fujun Yang^*

• Weihai Municipal Hospital, Affiliated to Shandong University, Weihai, China

HER2 (ERBB2) mutations, particularly exon 20 insertions, are rare but actionable oncogenic drivers in non-small cell lung cancer (NSCLC). Pyrotinib, an oral irreversible pan-ErbB tyrosine kinase inhibitor, has shown promising efficacy in previously treated HER2-mutant NSCLC, but its role in the first-line setting remains unclear. We report a case of a 61-year-old woman with stage IVB lung adenocarcinoma harboring an ERBB2 exon 20 insertion (p.Y772_A775dup) and a concurrent EGFR mutation, who was treated with first-line pyrotinib monotherapy. She achieved a partial response within one month and has maintained disease control for over 31 months, with only mild intermittent diarrhea. This case provides real-world evidence supporting the potential of pyrotinib as an effective first-line treatment for HER2-mutant NSCLC, particularly in patients with the Y772_A775dup variant and concurrent EGFR alterations, and highlights the need for further clinical investigation in this setting.