Sacituzumab Tirumotecan in EGFR-TKI–Resistant, EGFR -Mutated Advanced NSCLC

作者：Wenfeng Fang, Lin Wu, Xiangjiao Meng, Yu Yao, Wei Zuo, Wenxiu Yao, Yanyan Xie, Yu Zhang, Jiuwei Cui, Yongchang Zhang, Xingya Li, Wu Zhuang, Jian Hong Fang, Qiming Wang, Wei Jiang, Kai Li, Yuju Bai, Yongzhong Luo, Fang Ma, Yan Yu, Wei Zheng, Zhentian Liu, Bin Yang, Rui Ma, Yong Fang, Runxiang Yang, Liyan Jiang, Jie Hu, Jiacheng Yang, Yina Diao, Xiaoping Jin, Junyou Ge, Yun-Peng Yang, Li Zhang · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2512071 · 被引用次数：71 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Lung Cancer Diagnosis and Treatment

BACKGROUND: -mutated non-small-cell lung cancer (NSCLC) that has progressed after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy. METHODS: -mutated locally advanced or metastatic nonsquamous NSCLC that had progressed after EGFR-TKI therapy. The patients were randomly assigned, in a 1:1 ratio, to receive sac-TMT monotherapy or pemetrexed plus platinum-based chemotherapy. The primary end point was progression-free survival as assessed by blinded independent review. Overall survival was a hierarchically tested key secondary end point. In the interim analysis of progression-free survival as assessed by blinded independent review, sac-TMT monotherapy met the prespecified criterion for significance (two-sided P<0.0001); we report here the prespecified final analysis of progression-free survival and the preplanned interim analysis of overall survival. RESULTS: Overall, 376 patients underwent randomization, with 188 assigned to each group. After a median follow-up of 18.9 months, the median progression-free survival was 8.3 months in the sac-TMT group and 4.3 months in the chemotherapy group (hazard ratio for disease progression or death, 0.49; 95% confidence interval [CI], 0.39 to 0.62). Overall survival was significantly longer with sac-TMT than with chemotherapy (hazard ratio for death, 0.60; 95% CI, 0.44 to 0.82; two-sided P = 0.001); 18-month overall survival was 65.8% and 48.0%, respectively. Treatment-related adv...