已发表论文

克唑替尼具有良好的疗效,除了通过下一代测序鉴定出 ROS1 重排的非小细胞肺癌伴随的突变

 

Authors Zeng L, Li Y, Xiao L, Xiong Y, Liu L, Jiang W, Heng J, Qu J, Yang N, Zhang Y

Received 14 June 2018

Accepted for publication 17 September 2018

Published 15 October 2018 Volume 2018:11 Pages 6937—6945

DOI https://doi.org/10.2147/OTT.S176273

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Introduction: Data of standard tyrosine kinase inhibitor (TKI) treatment outcome in next-generation sequencing (NGS)-identified ROS1-rearranged non-small-cell lung cancer (NSCLC) were rare. Thus, it is practical and necessary to evaluate the efficacy and influential factors of crizotinib in real-world practice.
Patients and methods: A total of 1,466 NSCLC patients with positive targeted NGS test results from September 2015 to January 2018 were enrolled in this real-world retrospective study. Twenty-two patients had ROS1 rearrangement detected by NGS. The efficacy and safety of crizotinib were evaluated. Subgroups of concomitant mutations, brain metastasis, and fusion variants were also analyzed.
Results: Among all the patients, the occurrence rate of ROS1 rearrangement was 1.5% (22 of 1,466). Ten ROS1 fusion partners were detected, and the most common variant was CD74, which accounted for 50% (11 of 22). Five patients were found to carry dual ROS1 fusion partners, and 23% (5 of 22) of patients were detected with concomitant mutations, including TP53&PIK3CA&mTOR mutation, TP53&CDKN2A mutation, TP53&BRCA2 mutation, ALK missense mutation (p.R311H), and MET amplification. Among 22 patients with ROS1-rearranged NSCLC, 20 patients were diagnosed at stage IV, and 19 patients received crizotinib treatment. The average follow-up period was 16 months. The overall response rate (ORR) of crizotinib in unselected crizotinib-treated patients was 89%, and the median progression-free survival time (mPFS) was 13.6 months. It was shown that NSCLC patients with exclusive ROS1 rearrangement had a longer PFS than those carrying concomitant mutations (15.5 vs 8.5 months, =0.0213). There were no newly occurring intolerant adverse events in this study.
Conclusion: Crizotinib is highly effective in NGS-identified ROS1-rearranged advanced NSCLC in real-word clinical practice, and the data are consistent with previous clinical trials applying fluorescence in situ hybridization/real-time PCR for ROS1 companion diagnosis. Concomitant mutations may not be rare and may deteriorate the PFS of crizotinib in patients with ROS1-rearranged NSCLC.
Keywords: ROS1, next-generation sequencing, crizotinib, concomitant mutation, NSCLC, efficacy, TP53, safety




Figure 2 (A) PFS in 19 individual patients with ROS1-rearranged NSCLC treated with...