title: 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.
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. © 2017 American Cancer Society.
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Limin
authors.identifier: http://orcid.org/0000-0002-5605-7204
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xi
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shijia
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Su
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D044466:Asian People / Q000235:genetics; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D000077547:Crizotinib; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases
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)