Real-world treatment patterns and outcomes of HER2-altered NSCLC in China: A retrospective multi-center study (CHAPTER Study).

Abstract

e20502 Background: The HER2-targeted therapy trastuzumab deruxtecan (T-DXd) was approved for use in China in 2024, providing a novel option for patients with HER2-mutant non-small cell lung cancer (NSCLC). Despite its approval, data on treatment patterns and clinical outcomes in real-world settings remain scarce. This study aimed to analyze real-world treatment patterns and outcomes in HER2-mutant NSCLC, providing a foundation for optimizing HER2-targeted therapies in clinical practice. Methods: This retrospective analysis included clinical data from HER2-mutant NSCLC patients treated across four medical centers (Peking University Cancer Hospital & Institute, Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, The second affiliated hospital of Dalian medical university and The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital) between December 2015 and April 30, 2025. Statistical analyses were performed using SPSS software and included log-rank tests, Kaplan-Meier survival analyses, univariate and multivariate models, and Clopper-Pearson interval estimation. Results: 404 patients with HER2-altered NSCLC were included, of whom 49.75% (201/404) had HER2 exon 20 insertion mutations. Among patients harboring HER2 mutations (with or without amplification) receiving first-line therapy, trastuzumab deruxtecan (T-DXd) monotherapy achieved a median real-world progression-free survival (rwPFS) of 19.40 months (N = 11), which was significantly longer than chemotherapy (N = 34, 5.90 months), immunotherapy-based regimens (N = 106, 8.20 months), non-T-DXd HER2-targeted therapy (N = 25, 6.07 months), and anti-angiogenic based therapy (N = 44, 8.47 months) (P = 0.04). For second-line therapy, the median rwPFS of T-DXd monotherapy (N = 25, 10.13 months) was numerically longer than chemotherapy (N = 11, 3.90 months) and IO-based therapy (N = 28, 6.03 months) (P = 0.25). Conclusions: This is the largest real-world cohort study of HER2-mutant NSCLC to date. Real-world treatment strategies for HER2-mutant NSCLC patients are highly variable. T-DXd demonstrated the most favorable outcomes in both the first-line and second-line settings, showing superior effectiveness compared to other available treatments. These findings underscore the potential of T-DXd as a key therapeutic option for HER2-mutant NSCLC patients. Future studies are warranted to further validate these real-world outcomes and explore optimal therapeutic strategies.