AUTHOR=Ke Zhenyu , Yang Hongbo , Xing Meng , Bi Shasha , Yang Fujun 

TITLE=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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1637973

DOI=10.3389/fonc.2025.1637973

ISSN=2234-943X

ABSTRACT=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.