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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

5671 - The landscape of NTRK fusions in Chinese solid tumor patients

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

Presenters

Qi Ling

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

Q. Ling1, B. Li2, X. Wu3, H. Wang4, Y. Shen5, M. Xiao6, Z. Yang6, R. Ma7, D. Chen8, H. Chen9, X. Dong8, W. Wang10, M. Yao7

Author affiliations

  • 1 Department Of Hepatobiliary & Pancreatic Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 - Hangzhou/CN
  • 2 Department Of General Medicine, Affiliated Tumor Hospital of Guangxi Medical University, 530021 - Nanning/CN
  • 3 Department Of Thoracic Surgery, Nanfang Hospital, 510515 - Guangzhou/CN
  • 4 Respiratory Oncology Department, Cancer Hospital of Shantou University Medical College, 515000 - Shantou/CN
  • 5 Department Of Gynecology, Zhongda Hospital, Medical School, Southeast University, 210009 - Nanjing/CN
  • 6 Department Of Hepatobiliary & Pancreatic Surgery, Shu Lan (Hangzhou) Hospital, Zhejiang University International Hospital, 310000 - Hangzhou/CN
  • 7 Medical Department, OrigiMed, 200000 - Shanghai/CN
  • 8 Department Of Pathology, OrigiMed, 200000 - Shanghai/CN
  • 9 Department Of Bioinformatics, OrigiMed, 200000 - Shanghai/CN
  • 10 Department Of Cancer Immunology, OrigiMed, 200000 - Shanghai/CN
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Resources

Abstract 5671

Background

NTRK gene fusions resulting in the elevated expression of TRK kinases were discovered in a wide variety of tumor types but generally at a low frequency. TRK inhibitors such as LOXO-101 and entrectinib had remarkable and durable antitumor activities in patients (pts) with TRK fusion-positive cancers, regardless of age or tumor type.

Methods

FFPE tumor samples of over 3700 Chinese solid tumor pts were collected for NGS-based assay. We measured the gene fusions, mutations, and copy number alterations in tumor tissue against matched blood. Pan-Trk IHC testing was performed on five NTRK1 fusions.

Results

12 pts were idendified as NTRK fusion positive, which accounted to approximately 0.3% of the Chinese solid tumor pts in our cohort. Seven out of 12 pts harbored NTRK1 fusions with 6 partners, and the remaining ones were NTRK3 fusions with 2 partners. The half fusions with novel partner genes or breakpoints were defined as likely fusions. The tumor types of pts with NTRK fusions included NSCLC, colorectal cancer (CRC), prostate cancer and fibrosarcoma. NTRK fusions were more likely t occur in NSCLC and CRC, which accouted for 0.3% and 1.4%, respectively. Three predicted likely fusions and two known fusions were selected to perform pan-Trk IHC assay, and four were IHC positive. One known TPR-NTRK1 fusion not detected by IHC, which highlighted the necessity to use NGS to detect NTRK fusions due to higher sensitivity and capability. NTRK fusions were not always mutually exclusive with driver mutations. Three lung cancer pts with NTRK fusions also harbored EGFR-sensitive mutations.Table: 75P

Gene fusionCancer typeIHCPathogenic
NTRK1
TPM3 exon10-NTRK1 exon8Colorectal cancerPositiveLikely
IRF2BP2 exon1-NTRK1 exon8Prostate cancerPositiveLikely
PRDX1 exon5-NTRK1 exon12Lung adenocarcinomaPositiveLikely
LMNA exon2-NTRK1 exon11FibrosarcomaPositiveKnown
TPR exon21-NTRK1 exon 9Lung adenocarcinomaNegativeKnown
TPM3 exon10-NTRK1 exon8Colorectal cancerNALikely
AMOTL2 exon6-NTRK1 exon12Lung adenocarcinomaNALikely
NTRK3
ETV6 exon5 -NTRK3 exon15Colorectal cancerNAKnown
ETV6 exon5 -NTRK3 exon15Colorectal cancerNAKnown
ETV6 exon5 -NTRK3 exon15Squamous cell lung cancerNAKnown
ETV6 exon4 -NTRK3 exon14Small cell lung cancerNAKnown
AKAP13 exon3-NTRK3 exon14Lung adenocarcinomaNALikely

Conclusions

This study revealed NTRK fuisons in approximately 0.3% of Chinese solid tumor pts for the first time. The NTRK gene fusions more commonly occurred in NSCLC (0.3%) and CRC (1.4%), but may occur with other targetable alterations such as EGFR-activating mutations. NGS panel sequencing showed the advantage of detecting NTRK fusion and providing structure information of partners which could potentially guide more precise treatment options.

Clinical trial identification

Legal entity responsible for the study

OrigiMed.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

R. Ma, D. Chen, H. Chen, X. Dong, W. Wang, M. Yao: Employee: OrigiMed. All other authors have declared no conflicts of interest.

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