Combination regimens as potential treatment of non-small-cell lung cancer patients with HER2 mutation in the real world: a multicenter study.

BACKGROUND: Non-small-cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) mutations poses significant treatment challenges. While chemotherapy combined with immunotherapy or anti-angiogenic therapy has been explored, no standardized regimen exists for these patients. This study aims to evaluate the efficacy of different treatment regimens for HER2-mutated NSCLC. OBJECTIVES: Our study aimed to investigate the survival among NSCLC patients with HER2 mutation who received various treatment regimens in real-world settings, providing insights and guidance for clinical practice. DESIGNS: Survival analyses were conducted on patients who underwent different treatment regimens, including chemotherapy, immunotherapy, tyrosine kinase inhibitors (TKIs), and combination therapies, to evaluate their effectiveness. METHODS: This retrospective study included 118 patients diagnosed with HER2 mutations through next-generation sequencing at Zhejiang Cancer Hospital and Jinling Hospital affiliated with Nanjing University Medical School from September 2017 to December 2024. Data on treatment regimens and clinical outcomes, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), were collected. Kaplan-Meier analysis estimated PFS and OS, and Cox regression identified factors influencing PFS. RESULTS: Among the 118 patients, ORR and DCR were 22.9% and 58.5%, respectively. Median PFS and OS were 7.3 and 44.9 months, respectively. Combination therapies significantly improved PFS compared to single chemotherapy or immunotherapy or TKIs group (7.8 vs 5.3 months, p = 0.001). Patients with brain metastases also showed better PFS with combination therapies (7.8 vs 2.8 months, p = 0.001). The chemotherapy, immunotherapy, and anti-angiogenic therapy combination (C + I + A) yielded the best outcomes, with a PFS of 16.3 months. Cox regression revealed treatment regimen as the only factor significantly influencing PFS. CONCLUSION: Combination regimens, especially C + I + A, significantly improve PFS and offer superior therapeutic benefits for patients with HER2-mutated NSCLC compared to single chemotherapy or immunotherapy or TKIs treatments.