Autor: |
Si-Yang Maggie Liu, Xiao-Rong Dong, Zhen Wang, Yingying Du, Jiu-Wei Cui, Qian Chu, Bing-Fei Xu, Ming-Ying Zheng, Jia-Yi Deng, Chang Lu, Xue-Wu Wei, Yang-Si Li, Mei-Mei Zheng, Ming-Yi Yang, Jie Huang, Anna Li, Xiao-Yan Bai, Yue-Li Sun, Chong-Rui Xu, Bin-Chao Wang, Hua-Jun Chen, Jin-Ji Yang, Hong-Hong Yan, Wen-Zhao Zhong, Qing Zhou, Yi-Long Wu |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
EClinicalMedicine, Vol 64, Iss , Pp 102238- (2023) |
Druh dokumentu: |
article |
ISSN: |
2589-5370 |
DOI: |
10.1016/j.eclinm.2023.102238 |
Popis: |
Summary: Background: Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration. Methods: We initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm assessed the efficacy and safety of AZD3759 in untreated EGFR-mutated NSCLC with CNS metastases. The primary objective was the objective response rate (ORR). Simon’s minimax two-stage design was used to calculate the sample size. Dose optimal selection was performed using 200- and 300-mg bid cohorts. Findings: Between Oct 18, 2018 and Sep 14, 2020, 30 patients received AZD3759 at 200 mg (n = 15) or 300 mg (n = 15) bid. At data cutoff (Dec 31, 2022), median follow-up was 35.4 months. The primary endpoint was reached, with a confirmed ORR of 70% (21/30) (200 mg, 80%; 300 mg, 60%). The median progression-free survival was 12.9 months (200 mg, 15.8 months; 300 mg, 10.7 months). Grade 3 or 4 treatment-related adverse events occurred in 73% (22/30) of the patients (200 mg: 60%; 300 mg: 87%). 59% (10/17) of the patients developed a T790M mutation at disease progression. The median overall survival was 33.7 months, and 34.1 months and 25.3 months in patient treated with or without osimertinib in a later-line setting, respectively. Interpretation: AZD3759 showed promising efficacy and tolerable safety as a first-line therapy in EGFR-mutated NSCLC with CNS metastases. The 200-mg bid cohort had better clinical outcomes. Sequential use of AZD3759 and third-generation EGFR-TKIs represents a new option. Funding: Chinese Thoracic Oncology Group (CTONG). |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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