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Targeted Oncology

, Volume 14, Issue 2, pp 159–168 | Cite as

Distribution of ALK Fusion Variants and Correlation with Clinical Outcomes in Chinese Patients with Non-Small Cell Lung Cancer Treated with Crizotinib

  • Yudong Su
  • Xiang Long
  • Yang Song
  • Peng Chen
  • Shanqing Li
  • Huaxia Yang
  • Pancheng Wu
  • Yanyu Wang
  • Zhongxing Bing
  • Zhili Cao
  • Lei Cao
  • Yijun Wu
  • Zhe Zhang
  • Jing Liu
  • Bing Li
  • Jianxing Xiang
  • Ke Ma
  • Tengfei Zhang
  • Lu Zhang
  • Xinru Mao
  • Hao Liu
  • Puyuan XingEmail author
  • Naixin LiangEmail author
Original Research Article

Abstract

Background

ALK-rearranged non-small cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Crizotinib, a US Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treating ALK-rearranged NSCLC, has shown remarkable response in ALK-positive NSCLC. However, heterogeneity of clinical responses exists among different ALK fusion partners. Several small studies have investigated the correlation between fusion partners and efficacy, but not yielded consistent results.

Objective

We investigated the prevalence of ALK rearrangements in a Chinese NSCLC population, and correlated clinical outcomes of crizotinib with different ALK partners/variants.

Patients and methods

We retrospectively reviewed genomic profiling and clinical data of 110 ALK-rearranged NSCLC patients from five centers. The clinical response to crizotinib and survival data in ALK-positive patients was retrospectively analyzed.

Results

A total of 134 ALK rearrangements with 39 partners were identified in 110 patients (5.6%) among a cohort of 1971 NSCLC patients. The most frequently occurring ALK fusion partner was EML4, which was identified in 71.6% (96/134) of all of the rearrangements in 87.3% (96/110) patients, and with variant 3 (41/96, 42.7%) as the main variant type. No statistically significant differences in terms of progression-free survival (PFS) and overall survival (OS) were found between EML4-ALK and non-EML4-ALK NSCLC patients in our cohort (PFS, p = 0.207; OS, p = 0.678). Outcomes did not differ significantly between patients above and below 40 years of age (PFS, p = 0.427; OS, p = 0.686), nor between patients treated with crizotinib in different lines of therapy (PFS, p = 0.171; OS, p = 0.922). For EML4-ALK-positive NSCLC (n = 96), patients harboring variant 3 or variant 5 displayed significantly lower PFS and OS than those with other variants (PFS, 8.6 vs. 11.3 months, p = 0.046; OS, 31.0 vs. 37.6 months, p = 0.026). In addition, patients with a single EML4-ALK rearrangement event displayed favorable PFS (10.0 vs. 7.2 months, p = 0.040) and OS (36.0 vs. 20.0 months, p = 0.029) compared to those harboring multiple ALK rearrangements.

Conclusions

This study illustrates the patterns of ALK fusion variants present in Chinese NSCLC patients and might help explain heterogeneous clinical outcomes to crizotinib treatment according to different ALK fusion variants.

Notes

Acknowledgements

We would like to acknowledge all of the patients and their families for their contributions to this study.

Compliance with Ethical Standards

Funding

This study was funded by Beijing Natural Science Foundation (7182132), Major projects of the Beijing Municipal Science and Technology Commission (Z171100002017013), Capital Special Project for Featured Clinical Application (Z151100004015157), The Peking Union Medical College Hospital Youth Fund (PUMCH-2016-2.25, HI626500), PUMC Special Youth Teacher Project (2014zlgc0717), PUMC Special Youth Teacher Project (2014zlgc0135), Science and Technique Foundation of Tianjin Public Health Bureau (No.2015KZ085), and The Clinical Trial Foundation of Tianjin Tumor Hospital (No.C1712).

Conflict of interest

Yudong Su, Xiang Long, Yang Song, Peng Chen, Shanqing Li, Huaxia Yang, Pancheng Wu, Yanyu Wang, Zhongxing Bing, Zhili Cao, Lei Cao, Yijun Wu, Zhe Zhang, Jing Liu, Bing Li, Jianxing Xiang, Ke Ma, Tengfei Zhang, Lu Zhang, Xinru Mao, Hao Liu, Puyuan Xing and Naixin Liang declare that they have no conflicts of interest that might be relevant to the contents of this article.

Supplementary material

11523_2019_631_MOESM1_ESM.pdf (313 kb)
Supplementary material 1 (PDF 314 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Yudong Su
    • 1
  • Xiang Long
    • 2
  • Yang Song
    • 3
  • Peng Chen
    • 1
  • Shanqing Li
    • 3
  • Huaxia Yang
    • 4
  • Pancheng Wu
    • 3
  • Yanyu Wang
    • 3
  • Zhongxing Bing
    • 3
  • Zhili Cao
    • 3
  • Lei Cao
    • 3
  • Yijun Wu
    • 3
  • Zhe Zhang
    • 5
  • Jing Liu
    • 5
  • Bing Li
    • 5
  • Jianxing Xiang
    • 5
  • Ke Ma
    • 5
  • Tengfei Zhang
    • 5
  • Lu Zhang
    • 5
  • Xinru Mao
    • 5
  • Hao Liu
    • 5
  • Puyuan Xing
    • 6
    Email author
  • Naixin Liang
    • 3
    Email author
  1. 1.Key Laboratory of Cancer Prevention and Therapy, Department of Thoracic Medical Oncology, Lung Cancer Diagnosis and Treatment CenterTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjinChina
  2. 2.Department of Respiratory MedicinePeking University Shenzhen HospitalShenzhenChina
  3. 3.Department of Thoracic Surgery, Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
  4. 4.Department of Rheumatology and Immunology, Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
  5. 5.Burning Rock BiotechGuangzhouChina
  6. 6.National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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