Evidence of Efficacy for Neoadjuvant Immunochemotherapy in a Rare Subgroup: Two Cases of Pathological Complete Response in Locally Advanced HER2-Mutant NSCLC.

INTRODUCTION: Neoadjuvant immunochemotherapy (nICT) has been recommended as the standard regimen for locally advanced non-small cell lung cancer (NSCLC) without actionable genomic alterations. However, the efficacy of nICT for patients harboring human epidermal growth factor receptor 2 (HER2) mutation remains uncertain. Here, we report two cases with locally advanced HER2-mutant NSCLC who received nICT followed by radical surgery. CASE PRESENTATION: This study reports 2 cases of patients with resectable HER2-mutant NSCLC in stage III. Both patients were 67-year-old males who received nICT followed by radical surgery. Postoperative pathological evaluation confirmed pathological complete response in both patients. As of the last follow-up in June 30, 2025, neither patient had evidence of disease recurrence, with disease-free survival exceeding 36 months in both cases, demonstrating favorable therapeutic response and sustained outcomes. CONCLUSION: nICT for locally advanced NSCLC harboring HER2 mutations demonstrated promising efficacy and safety. These cases may be suggestive of the wider applicability of nICT in the perioperative management of this molecularly defined NSCLC subset.