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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

850 - A multicenter study of mutational profiling of Chinese ALK+ non-small cell lung cancer patients with required resistant to crizotinib using next generation sequencing

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Targeted Therapy

Tumour Site

Presenters

Chunwei Xu

Citation

Annals of Oncology (2018) 29 (suppl_8): viii493-viii547. 10.1093/annonc/mdy292

Authors

C. Xu1, W. Wang2, W. Zhuang3, Z. Song2, Y. Zhu4, G. Chen1, M. Fang2, T. Lv5, Y. Song5

Author affiliations

  • 1 Pathology, Fujian Cancer Hospital, 350014 - Fuzhou/CN
  • 2 Chemotherapy, Zhejiang Cancer Hospital, 310022 - Hangzhou/CN
  • 3 Medical Thoracic Oncology, Fujian Cancer Hospital, 350014 - Fuzhou/CN
  • 4 Thoracic Disease Center, Zhejiang Rongjun Hospital, 314000 - Jiaxing/CN
  • 5 Respiratory Medicine, Jinling Hospital, 210002 - Nanjing/CN
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Resources

Abstract 850

Background

Anaplastic lymphoma kinase (ALK) rearrangements define a distinct molecular subtype of non-small cell lung cancer. Recently, the therapeutic landscape for advanced ALK+ NSCLC has been transformed by the development of increasingly potent and selective ALK inhibitors. Crizotinib was the first ALK inhibitor to enter clinical development. The mechanism of acquired resistance to crizotinib for the patients with ALK+ NSCLC is not yet fully identified. In this study, we performed mutational profiling in a cohort of 42 ALK+NSCLC patients at diagnosis and following acquired resistance to crizotinib using targeted NGS.

Methods

A total of 42 patients with stage IIIb-IV ALK+ NSCLC underwent tumor biopsies or blood withdrawal by the time of acquiring resistance to crizotinib, including 19 formalin-fixed paraffin-embedded (FFPE) samples, 12 serum samples and 11 serous effusions. We used targeted NGS to detect the gene status of patients.

Results

In total, we identified 92 genetic alterations with a median of 2.2 mutations per patient. 83% of patients still exhibit fusions, and 29% of patients acquired ALK point mutations. Besides other known resistance mechanisms, we identified KRAS mutations in 14% of patients, and EGFR mutations in 12%. Interestingly, we also observed IGF1R, GPR133, CDH18and HSD17B3 mutations in ALK point mutation-negative patients, which were restricted to crizotinib resistance.

Conclusions

Our study uncovered mutational profiles of ALK+NSCLC patients with crizotinib resistance with potential therapeutic implications, and this study also comprehensively depicted the genetic landscape in a Chinese ALK+NSCLC population resistant to crizotinib. Our analysis demonstrates new perspectives for further study of resistance and suggests corresponding relevant tactics against the challenge of disease progression.

Clinical trial identification

Legal entity responsible for the study

Chunwei Xu.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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