학술논문
Updated overall survival and circulating tumor DNA analysis of ensartinib for crizotinib‐refractory ALK‐positive NSCLC from a phase II study
Document Type
article
Author
Jing Zheng; Tao Wang; Yunpeng Yang; Jie Huang; Jifeng Feng; Wu Zhuang; Jianhua Chen; Jun Zhao; Wei Zhong; Yanqiu Zhao; Yiping Zhang; Yong Song; Yi Hu; Zhuang Yu; Youling Gong; Yuan Chen; Feng Ye; Shucai Zhang; Lejie Cao; Yun Fan; Gang Wu; Yubiao Guo; Chengzhi Zhou; Kewei Ma; Jian Fang; Weineng Feng; Yunpeng Liu; Zhendong Zheng; Gaofeng Li; Huijie Wang; Shundong Cang; Ning Wu; Wei Song; Xiaoqing Liu; Shijun Zhao; Lieming Ding; Giovanni Selvaggi; Yang Wang; Shanshan Xiao; Qian Wang; Zhilin Shen; Jianya Zhou; Jianying Zhou; Li Zhang
Source
Cancer Communications, Vol 44, Iss 4, Pp 455-468 (2024)
Subject
Language
English
ISSN
2523-3548
Abstract
Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.