biostudies-literatureXiang YThis study is supported by the National Natural Science Foundation of China148https://www.ebi.ac.uk/biostudies/studies/S-EPMC11941541biostudies-literatureUnknown32(3)Background: HER2 mutations are rare driver events in advanced NSCLC, with limited relief from current targeted therapies. This study aimed to characterize the molecular features of HER2-mutant NSCLC and to evaluate the clinical efficacy of pyrotinib-based combination therapy as a first-line treatment, providing evidence for optimizing treatment strategies. Methods: NSCLC patients diagnosed at Jiangsu Province People's Hospital from 2016 to 2024 were enrolled. HER2-positive cases were screened by IHC/FISH and further profiled by NGS. Treatment response was assessed by RECIST 1.1, and survival analysis was performed using Kaplan-Meier and log-rank tests. Results: Among 144 HER2-mutant NSCLC cases confirmed by NGS, 10 insertion mutations, 26 missense mutations, and 2 fusiCurrent oncology (Toronto, Ont.)First-Line Pyrotinib Combination Therapy for HER2-Mutated Advanced NSCLC: A Retrospective Cohort Analysis.PMC11941541(82172708)Lu KLiu JWang QSun AZeng LXiang YZhang MfalseFirst-Line Pyrotinib Combination Therapy for HER2-Mutated Advanced NSCLC: A Retrospective Cohort Analysis.Background: HER2 mutations are rare driver events in advanced NSCLC, with limited relief from current targeted therapies. This study aimed to characterize the molecular features of HER2-mutant NSCLC and to evaluate the clinical efficacy of pyrotinib-based combination therapy as a first-line treatment, providing evidence for optimizing treatment strategies. Methods: NSCLC patients diagnosed at Jiangsu Province People's Hospital from 2016 to 2024 were enrolled. HER2-positive cases were screened by IHC/FISH and further profiled by NGS. Treatment response was assessed by RECIST 1.1, and survival analysis was performed using Kaplan-Meier and log-rank tests. Results: Among 144 HER2-mutant NSCLC cases confirmed by NGS, 10 insertion mutations, 26 missense mutations, and 2 fusi2025-01-01T00:00:00Z2025 Mar2025-07-05T03:05:29.209Z2025-07-05T03:05:29.209ZS-EPMC119415414013635210.3390/curroncol32030148