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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

2977 - Recurrent and Metastatic Carcinomas of the Lacrimal Gland: High Frequency of ERBB2 Driven Disease

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

Translational Research

Tumour Site

Presenters

Nicolas Girard

Citation

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

Authors

N. Girard1, R.J. Corona2, J. Chung3, S.Z. Millis3, L.M. Gay4, J.A. Elvin3, J. Vergilio3, S. Ramkissoon3, E. Severson3, S. Daniel3, J.K. Killian3, S.M. Ali3, A.B. Schrock5, V.A. Miller3, J.S. Ross6

Author affiliations

  • 1 Institut Du Thorax Curie Montsouris, Institut Curie, 75248 cedex5 - Paris/FR
  • 2 Medical Oncology, Upstate Medical University, 13210 - Syracuse/US
  • 3 Genetics, Foundation Medicine, Inc., Cambridge/US
  • 4 Pathology, Foundation Medicine, 02141 - Cambridge/US
  • 5 Genetics, Foundation Medicine, Inc., MA 02141 - Cambridge/US
  • 6 Medicine, SUNY Upstate Medical University, Syracuse/US
More

Resources

Abstract 2977

Background

Lacrimal gland carcinomas (LGC) are uncommon primary malignancies that have a propensity to recur locally but rarely undergo metastasis. We performed comprehensive genomic profiling (CGP) on a series of 12 LGC to uncover genomic alterations (GA) that could possibly be used to design novel routes to targeted and immunotherapies for these rare neoplasms.

Methods

From a series of 158,360 clinically advanced cancer cases, FFPE tissue samples from 12 cases of LGC underwent CGP to find base substitutions, short indels, copy number changes and gene fusions. Microsatellite instability (MSI) was determined on 114 loci andtumormutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and reported as mutations (mut) per megabase (Mb).

Results

The 12 LGC patients ranged in age from 34 to 76 years (median 61 years) and 67% of the patients were male. The LGC included 7 (58%) adenocarcinomas, 2 (17%) squamous cell carcinomas, 2 (17%) adenoid cystic carcinomas and 1 (8%) undifferentiated carcinomas. There were 1 (8%) grade 1, 8 (67%) grade 2 and 3 (25%) grade 3 tumors. 2 (17%) of LGC were stage III and 10 (83%) were stage IV at the time of sequencing. There were an average number of 4.25 GA per tumor. Three (25%) of the LGC featured ERBB2(HER2) gene amplification. One (33%) of the 3 ERBB2amplified LGC also featured TOP2A amplification. ERBB2copy numbers in the amplified LGC ranged from 5 to 35 copies. Additional potentially targetable GA included PTENand PIK3CAboth at 25%, NF1 at 17% and RET, BRCA2, FGFR3and NTRK3all at 8% of cases. No (0%) LGC were MSI-High and the median TMB was 4.3 mut/Mb (range 0 to 12 mut/Mb) with no (0%) of LGC having >20 mut/Mb.

Conclusions

The high frequency ofERBB2amplification in clinically advanced LGC is similar to that seen in the approved indications for breast and upper gastrointestinal carcinomas raising opportunities for anti-HER2 therapies for these patients. In addition, a smaller cohort of LGC patients have opportunities for other targeted therapies with TKIs directed at RET, FGFR3 and NTRK. Given the lack of MSI-high and high TMB in LGC, the opportunities for immunotherapies for these patients appears limited.

Clinical trial identification

Legal entity responsible for the study

Foundation Medicine, Inc, Cambridge, MA, USA.

Funding

Foundation Medicine Inc, Cambridge, MA, USA.

Editorial Acknowledgement

Disclosure

J. Chung, S.Z. Millis, L.M. Gay, J.A. Elvin, J-A. Vergilio, S. Ramkissoon, E. Severson, S. Daniel, J.K. Killian, S.M. Ali, A.B. Schrock, V.A. Miller: Employment: Foundation Medicine, Inc. All other authors have declared no conflicts of interest.

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