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Q. Zou



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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-006 - Effect of EML-Alk Fusion Variant and Fusion Abundance on the Efficacy of Crizotinib in Non-Small Cell Lung Cancer (ID 8552)

      09:30 - 16:00  |  Author(s): Q. Zou

      • Abstract

      Background:
      EML4-ALK fusion gene is a molecular subtype of non-small cell lung cancer (NSCLC), which is carcinogenic both in vitro and in vivo. Most of the EML4-ALK-positive NSCLC patients have effectively sensitivity with an ALK tyrosine kinase inhibitor (TKI), such as crizotinib. However, the treatment outcomes and duration of response are heterogeneous. EML4-ALK has several variants. The effects of ALK fusion variants on the efficacy of crizotinib is still unclear, although many scientists are committed to this work. In addition, we also unknown the effects of ALK variants allele fraction (AF) on the efficacy of crizotinib.

      Method:
      Among 54 patients with advanced NSCLC were treated with crizotinib as the first-line or further-line ALK-TKI between 2013 and 2017, eventually, we identified 48 patients whose the tumor samples were detected by IHC(38), FISH(2), NGS(5),PCR(1) and ARMS(2). Through retrospective analysis, we assumed the efficacy of crizotinib on the basis of the PFS according to the ALK variants and its allele fraction.

      Result:
      Among the 29 ALK-positive patients, the most common ALK variants was variant 1 in 13 patients (44.9%), followed by variant 3 in 7 patients (24.1%), variants 2 in 2 patients (6.9%), other variants in 7 patients (24.1%). We divided all variants into two subgroups: V1/3 and V2/others. We found 35.4% of the samples test results between the next generation sequencing (NGS) and hospital immunohistochemical were not concordence. Further analysis found that patients who did not match that PFS were shorter (p=0.036). By the NGS, we observed from the figure that the variant 2/others group, the median PFS had a longer trend than V1/3 group, although not statistically significant(p>0.05. The level of AF was no correlated with PFS (P=0.346).

      Conclusion:
      The above results show that next-generation sequencing (NGS) can identify ALK variants and AF, therefore, NGS can be used as a supplement to a detection method. The type of EML4-ALK fusion variants may has a certain correlation with PFS in patients who oral crizotinib treatment. Since the sample size of this study is small, we have not yielded accurate results and found only these phenomena. We believe that in the near future, most NSCLC patients can be detected by NGS detection of gene mutations, especially EML4-ALK fusion gene, and according the different of the fusion gene variant type which can be estimated the efficacy of the ALK-TKIs, to provide the basis of individualized treatment options for NSCLC patients.