Detection of Nonreciprocal/Reciprocal ALK Translocation as Poor Predictive Marker in Patients With First-Line Crizotinib-Treated ALK-Rearranged NSCLC

Yongchang Zhang, Liang Zeng, Chunhua Zhou, Yizhi Li, Lin Wu, Chen Xia, Wenjuan Jiang, Yijuan Hu, Dehua Liao, Lili Xiao, Li Liu, Haiyan Yang, Yi Xiong, Rui Guan, Analyn Lizaso, Aaron S. Mansfield, Nong Yang

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3 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalJournal of Thoracic Oncology
DOIs
StateAccepted/In press - 2020

Keywords

  • ALK
  • Biomarker
  • Crizotinib
  • Dual ALK fusion
  • Non-small cell lung cancer
  • Nonreciprocal/reciprocal ALK translocation

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    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, A. S., & Yang, N. (Accepted/In press). Detection of Nonreciprocal/Reciprocal ALK Translocation as Poor Predictive Marker in Patients With First-Line Crizotinib-Treated ALK-Rearranged NSCLC. Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2020.02.007