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Proffered Paper – NETs and endocrine tumours

1796 - Malignant Non-adrenal Paraganglioma (mPara) and Adrenal Pheochromocytoma (mPheo) a Comparative Comprehensive Genomic Profiling (CGP) Study

Date

29 Sep 2019

Session

Proffered Paper – NETs and endocrine tumours

Topics

Rare Cancers

Tumour Site

Neuroendocrine Neoplasms;  Genitourinary Cancers

Presenters

Gennady Bratslavsky

Citation

Annals of Oncology (2019) 30 (suppl_5): v194-v197. 10.1093/annonc/mdz245

Authors

G. Bratslavsky1, E.S. Sokol2, A. Necchi3, O. Shapiro1, J. Jacob1, N. Liu1, J.A. Elvin4, J. Vergilio4, J..K. Killian4, N. Ngo4, D. Lin4, S. Ramkissoon4, E. Severson4, S.M. Ali2, A.B. Schrock5, J. Chung2, P. Reddy6, B.M. Alexander2, V.A. Miller2, J.S. Ross7

Author affiliations

  • 1 Urology, Upstate Medical University, 13210 - Syracuse/US
  • 2 Clinical Development, Foundation Medicine, 02141 - Cambridge/US
  • 3 Medical Oncology, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, 20133 - Milan/IT
  • 4 Pathology, Foundation Medicine, 02141 - Cambridge/US
  • 5 Clinical Development, Foundation Medicine, MA 02141 - Cambridge/US
  • 6 Medical Affairs, Foundation Medicine, 02141 - Cambridge/US
  • 7 Pathology And Urology, Upstate Medical University, 13210 - Syracuse/US

Resources

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Abstract 1796

Background

We used CGP to compare the genomic alterations (GA) in mPara and mPheo to enable the search for potential therapy targets.

Methods

FFPE sections of 84 mPara and 44 mPheo underwent hybrid-capture based CGP. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and reported as mutations/Mb and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (DAKO 22C3 antibody).

Results

All patients had recurrent and/or metastatic disease. Patient ages were similar, but mPara featured significantly more male patients (Table). The GA/tumor frequency was low for both tumor types. The most frequent un-targetable GA were in SDHB, ATRX and TERT in mPara and ATRX, TP53 and SDHB in mPheo. The most frequent potentially targetable GA in mPara were in FGFR1 (7%, primarily amplifications) and NF1, PTEN, NF2 and CDK4 (all 2%) and for mPheo were in RET (9%, primarily fusions), NF1 (9%) and FGFR1 (5%). PBRM1 GA were found in only in 1% of mPara and 2% of mPheo. Germline mutations in known cancer predisposition genes were predicted in 38 (45%) mPara and 8 (18%) mPheo cases, predominantly involving the SDHA/B genes. The TMB and PD-L1 expression levels were similar in both tumor types and 0% of cases were associated with MSI High status.Table: 512O

mParamPheo
Number of Cases8444
Age in years (range)48 (10-80)52 (7-78)
Males/Females51/3323/21
GA per tumor[AS1]1.92.3
Most common Untargetable GASDHB (27%) ATRX (21%) TERT (18%) TP53 (7%) SDHA (7%)ATRX (25%) TP53 (21%) SDHB (13%) CTNNB1 (7%) VHL (7%) CDKN2A/2B, PIK3R2, NOTCH2 and MEN1 (all 5%)
Most common Targetable GAFGFR1 (7%) NF1 (2%) PTEN (2%) NF2 (2%) CDK4 (2%)RET (9%) NF1 (9%) FGFR1 (5%)
CD274 amplification0%0%
PBRM1 GA1%2%
MSI0%0%
Median TMB mut/Mb1.32.4
TMB > 10/20 mut/Mb6%/2%5%/0%
PD-L1 Expression low/high14%/0%0%/0%

Conclusions

mPara and mPheo feature similar GA with mPara more often associated with germline GA. Although the GA/tumor is relatively low for mPara and mPheo, CGP can reveal important potential therapy targets in both tumor types including RET, NF1 and FGFR1. Based on biomarker assessments, mPara and mPheo do not appear to have strong potential for responsiveness to immunotherapies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Foundation Medicine.

Funding

Foundation Medicine.

Disclosure

E.S. Sokol: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.A. Elvin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Vergilio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J..K. Killian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. N. Ngo: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. D. Lin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S. Ramkissoon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. E. Severson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S.M. Ali: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. A.B. Schrock: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Chung: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. P. Reddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. B.M. Alexander: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. V.A. Miller: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.S. Ross: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. All other authors have declared no conflicts of interest.

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