Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion-positive non–small cell lung cancer

Limin Zhang, Tao Jiang, Xuefei Li, Yan Wang, Chao Zhao, Sha Zhao, Lei Xi, Shijia Zhang, Xiaozhen Liu, Yijun Jia, Hui Yang, Jinpeng Shi, Chunxia Su, Shengxiang Ren, Caicun Zhou

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

BACKGROUND: The authors' previous study demonstrated that the B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (BCL2L11) (Bim) deletion polymorphism was associated with poor clinical response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with non–small cell lung cancer (NSCLC) with EGFR mutations. The objective of the current study was to investigate the impact of the Bim deletion polymorphism among patients with anaplastic lymphoma kinase (ALK)-positive or ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)-positive NSCLC who were treated with crizotinib. METHODS: A total of 55 patients with ALK-positive NSCLC and 14 patients with ROS1-positive NSCLC who were treated with crizotinib were enrolled into the current study. The Bim deletion polymorphism was analyzed by polymerase chain reaction. The clinical features of the Bim deletion polymorphism and its impact on the effect of crizotinib were investigated. RESULTS: The Bim deletion polymorphism was present in 9 of 69 patients with ALK-positive or ROS1-positive NSCLC (13.0%). There were no differences noted with regard to clinicopathological features between patients with and without the Bim deletion polymorphism. Patients with the Bim deletion polymorphism had a significantly shorter progression-free survival (PFS) and lower objective response rate compared with those without (median PFS, 182 days vs 377 days [P =.008]) (objective response rate, 44.4% vs 81.7% [P =.041]) in all populations. The significant difference in PFS was observed in patients with ALK-positive NSCLC (83 days vs 305 days [P =.0304]) compared with those with ROS1-positive NSCLC (218 days vs not reached [P =.082]). Multivariate analysis indicated that the Bim deletion polymorphism was an independent predictive factor for patients with ALK-positive NSCLC who were treated with crizotinib (hazard ratio, 4.786 [P =.006]). CONCLUSIONS: The Bim deletion polymorphism was found to be associated with poor clinical response to crizotinib in patients with ALK fusion-positive NSCLC. Cancer 2017;123:2927–35.

Original languageEnglish (US)
Pages (from-to)2927-2935
Number of pages9
JournalCancer
Volume123
Issue number15
DOIs
StatePublished - Aug 1 2017

Bibliographical note

Funding Information:
Supported in part by grants from the National Natural Science Foundation of China (grants 81672286, 81372392, and 81402486), key project of the Shanghai Municipal Commission of Health and Family Planning (grant 2013zyjb0401), and the Outstanding Young Physician Program of the Shanghai Municipal Commission of Health and Family Planning (grant XYQ2013097).

Keywords

  • B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (BCL2L11) (Bim)
  • ROS proto-oncogene 1
  • anaplastic lymphoma kinase (ALK)
  • crizotinib
  • non–small cell lung cancer
  • receptor tyrosine kinase (ROS1)

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