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ECB-ART-49877
J Thorac Oncol 2020 Jun 01;156:1027-1036. doi: 10.1016/j.jtho.2020.02.007.
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Detection of Nonreciprocal/Reciprocal ALK Translocation as Poor Predictive Marker in Patients With First-Line Crizotinib-Treated ALK-Rearranged NSCLC.

Zhang Y , Zeng L , Zhou C , Li Y , Wu L , Xia C , Jiang W , Hu Y , Liao D , Xiao L , Liu L , Yang H , Xiong Y , Guan R , Lizaso A , Mansfield AS , Yang N .


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INTRODUCTION: During nonreciprocal/reciprocal translocation process, 5'-anaplastic lymphoma kinase (ALK) sometimes gets retained in the genome and is detectable by next-generation sequencing; however, no study has investigated its clinical significance. Our study aimed to assess the impact of harboring 5'-ALK on the efficacy of crizotinib. METHODS: A total of 150 patients with next-generation sequencing-identified ALK-rearranged NSCLC from March 2014 to July 2018 at the Hunan Cancer Hospital were enrolled in this study. The efficacy of crizotinib as first-line therapy was evaluated in 112 patients according to the retention of 5'-ALK. RESULTS: Among the 150 patients with NSCLC, nonreciprocal/reciprocal translocation was detected in 18.7% (28 of 150), and 3'-ALK fusion alone was detected in 81.3% (122 of 150). Among the 112 patients who received first-line crizotinib, 89 had 3'-ALK fusion alone (79 echinoderm microtubule associated protein-like 4 [EML4]-ALK and 10 non-EML4-ALK), and 23 had nonreciprocal/reciprocal ALK translocation. Among the patients with nonreciprocal/reciprocal ALK translocation, three patients harbored dual concurrent 3'-ALK fusions. Patients with nonreciprocal/reciprocal ALK translocation had higher incidence of brain metastasis at baseline than those with 3'-ALK fusion alone (39.1% versus 13.4%, p = 0.028). Crizotinib-treated patients with nonreciprocal/reciprocal ALK translocation had significantly shorter median progression-free survival (PFS) compared with patients carrying 3'-ALK fusion alone (6.1 m versus 12.0 m, p = 0.001) or with EML4-ALK fusion alone (6.1 m versus 12.6 m, p = 0.001). Multivariate analysis revealed that harboring nonreciprocal/reciprocal ALK translocation was an independent predictor of worse PFS for crizotinib-treated ALK-rearranged NSCLC (p = 0.0046). CONCLUSIONS: Presence of nonreciprocal/reciprocal ALK translocation was predictive for worse PFS and greater likelihood of baseline brain metastases in patients with ALK-rearranged NSCLC who received first-line crizotinib.

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