Mutational profiling of Chinese ROS1 positive non-small cell lung cancer patients with required resistant to crizotinib by next generation sequencing

Sub-category:
Genetic Testing
Category:
Cancer Prevention, Hereditary Genetics, and
Epidemiology
Meeting:
2017 ASCO Annual Meeting
Abstract No:
e13120
Citation:
J Clin Oncol 35, 2017 (suppl; abstr e13120)
Author(s): Wen-xian Wang, Chunwei Xu, Meiyu Fang, You-cai Zhu, Yan-ping Chen, Yu Chen,Xing-hui Liao, Wu Zhuang, Gen Lin, Xiao-hui Chen, Yun-jian Huang, Hai-peng Xu, Kai-qi Du,Yan-Fang Guan, Xin Yi, Gang Chen, Tangfeng Lv, Yong Song; Zhejiang Cancer Hospital, Hangzhou,China; Fujian Cancer Hospital, Fuzhou, China; Zhejiang Rongjun Hospital, Jiaxing, China;Geneplus-Beijing, Beijing, China; Jinling Hospital, Medical School of Nanjing University, Nanjing,China; Nanjing General Hospital of Nanjing Military Command, Nanjing, China

Abstract Disclosures

Abstract

Background

The ROS1 rearrangement has been identified in 1%-2% of NSCLC cases, these patients would benefit from the inhibitor of crizotinib. But the resistance to crizotinib inevitably developed in the patients with ROS1+ NSCLC and shown a response to crizotinib initially. The mechanism of acquired resistance to crizotinib for the patients with ROS1+ NSCLC is not identified completely now. In this study, we performed mutational profiling in a cohort of 16 ROS1+NSCLC patients at diagnosis and acquired resistance to crizotinib using targeted NGS.

Methods

A total of 16 patients with stage IIIb-IV ROS1+ NSCLC were undergoing tumor biopsies or blood withdrawing by the time of acquiring resistance to crizotinib, including 4 formalin-fixed paraffin-embedded (FFPE) samples, 9 serum samples and 3 serous effusions. We used targeted NGS to detect genes status of patients.

Results
In total, we identified 62 genetic alterations with a median of 3.9 mutations per patient. 93% of patients still exhibit fusions, and 31% of patients acquired ROS1 required point mutations.Besides other known resistance mechanisms, we identified CDKN2A mutations in 19% of patients.Interestingly, we also observed TERT, PTPRD, NFE2L2 and OR5L2 mutations in ROS1 required point mutations negative patients, which were restricted to crizotinib resistance.

Conclusions
Our study uncovered mutational profiles of ROS1+NSCLC patients with crizotinib resistance with potential therapeutic implications, and this study also depicted the genetic landscapes comprehensively in Chinese ROS1+NSCLC population resistant to crizotinib. Our analysis demonstrates new perspectives for further study of resistance and putting forward corresponding relevant tactics against the challenge of disease progression.