Landscape of Next Generation Sequencing in Screening Accurate Benefit Population for First Line Crizotinib in ALK Rearranged Advanced Non-Small Cell Lung Cancer

Background: First line crizotinib response duration time differs with different detecting methods and fusion patterns in ALK-rearranged advanced non-small cell lung cancer (aNSCLC) patients. However, detecting methods choosing and accurate benefit population identification lack data to elucidate. Methods: 115 ALK-rearranged aNSCLC patients received first-line crizotinib form March 2014 to July 2018 in Hunan cancer hospital were enrolled in this study. Efficacy of crizotinib was evaluated categorized by different detecting methods and fusion partners. Findings: Among 115 first-line crizotinib treated ALK-rearranged aNSCLC patients; 86 patients (74.8%) were detected by next generation sequencing (NGS) while 29 patients (25.2%) by Ventana. 103 ALK fusion partners were detected in 86 NGS-identified ALK-rearranged patients and 18 partners were firstly reported. 16 in the 86 (18.6%) patients were found with dual fusion partners. The overall response rate (ORR) was 85.2% and the median progression-free survival time (mPFS) was 12.6 months. No significant difference of first line crizotinib efficacy was observed between NGS and Vantana groups (mPFS, 12m vs. 16m, p=0.183). Patients with dual ALK fusion partners have a significantly shorter mPFS compared with patients carrying single ALK fusion partner (6.1m vs. 12.8m, p=0.001). Patients with EML4 partners have a significantly longer mPFS compared with patients carrying non-EML4 fusion partners (14.1m vs. 6.5m, p=0.004). Conclusions: Ventana and NGS didn't confer significant difference in first-line crizotinib efficacy in ALK-rearranged aNSCLC patients. Dual ALK or non-EML4 fusion partners negatively contribute to first-line crizotinib efficacy in NSCLC. Comprehensive treatment strategies should be considered for theses subgroups of patients. Funding Statement: This work got financial support from the National Natural Science Foundation (NO.81401902 to Yongchang Zhang and NO.81501992 to Rui Guan) and Hunan Natural Science Foundation (2018RS3106 to Yongchang Zhang, 2018JJ2238 to Yongchang Zhang and 2017SK2134 to Nong Yang). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: Approval was obtained from the ethics committee of Hunan Cancer Hospital.