Crizotinib presented with promising efficacy but for concomitant mutation in next-generation sequencing-identified ROS1-rearranged non-small-cell lung cancer.

Abstract

IntroductionData 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 methodsA 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.ResultsAmong 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, P=0.0213). There were no newly occurring intolerant adverse events in this study.ConclusionCrizotinib 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.