Sevabertinib in Advanced HER2 -Mutant Non–Small-Cell Lung Cancer

作者：Xiuning Le, Tae Min Kim, Herbert H. Loong, Arsela Prelaj, Boon Cher Goh, Lin Li, Yong Fang, Shun Lu, Xiaorong Dong, Lin Wu, Yuki Shinno, Gennaro Daniele, Tsung‐Ying Yang, Hye Ryun Kim, G. Ruiter, Jun Zhao, Silvia Novello, Liyun Miao, Pasi A. Jänne, Kōichi Goto, Dominik Rüttinger, Tine Descamps, Jan C. Brase, Weichao Bao, Rui Li, Nicoletta Brega, Paolo Grassi, Nicolas Girard, Daniel Shao-Weng Tan · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2511065 · 被引用次数：52 · 研究领域：Lung Cancer Treatments and Mutations、HER2/EGFR in Cancer Research、Cancer Immunotherapy and Biomarkers

BACKGROUND: gene mutations occur in 2 to 4% of patients with non-small-cell lung cancer (NSCLC). Sevabertinib is an oral, reversible tyrosine kinase inhibitor that has shown anti-HER2 activity in preclinical models. METHODS: -mutant NSCLC. Three cohorts were defined according to previous therapy: cohort D comprised previously treated patients who had not received HER2-targeted therapy; cohort E, patients who had previously received HER2-directed antibody-drug conjugates; and cohort F, patients who had not previously received treatment. The primary end point was an objective response, as assessed by blinded independent central review. Secondary end points were duration of response and progression-free survival. RESULTS: A total of 209 patients received sevabertinib (as of June 27, 2025, the data-cutoff date); the median duration of follow-up was 13.8 months in cohort D, 11.7 months in cohort E, and 9.9 months in cohort F. Among 81 patients in cohort D, an objective response was observed in 64% (95% confidence interval [CI], 53 to 75); the median duration of response was 9.2 months (95% CI, 6.3 to 13.5), and the median progression-free survival was 8.3 months (95% CI, 6.9 to 12.3). Among 55 patients in cohort E, an objective response was observed in 38% (95% CI, 25 to 52); the median duration of response was 8.5 months, and the median progression-free survival was 5.5 months. Among 73 patients in cohort F, an objective response was observed in 71% (95% CI, 59 to 81), and the me...