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Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies

Date

10 Oct 2016

Session

Head and neck cancers

Presenters

Laurie Gay

Citation

Annals of Oncology (2016) 27 (6): 328-350. 10.1093/annonc/mdw376

Authors

L.M. Gay1, J.S. Ross2, K. Wang3, J. Vergilio1, J. Suh1, S. Ramkissoon1, D. Bowles4, H. Serracino4, J. Russell5, S. Ali6, V. Miller6, P. Stephens7, J.A. Elvin1

Author affiliations

  • 1 Pathology, Foundation Medicine, Inc., 02141 - Cambridge/US
  • 2 Pathology, Albany Medical Center, 12208 - Albany/US
  • 3 Genetics, Zhejiang Cancer Hospital, 310009 - Hangzhou/CN
  • 4 Division Of Medical Oncology, University of Colorado Denver, 80045 - Denver/US
  • 5 Medical Oncology, Moffitt Cancer Center, 33612 - Tampa/US
  • 6 Clinical Development, Foundation Medicine, Inc., 02141 - Cambridge/US
  • 7 Clinical Genomics, Foundation Medicine, Inc., 02141 - Cambridge/US
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Abstract 1192

Background

Salivary gland carcinomas (SGC) have a wide diversity of histologic subtypes with variable clinical aggressiveness and response to local and systemic therapies. We queried whether comprehensive genomic profiling (CGP) could define tumor subtypes and uncover clinically relevant genomic alterations (CRGA), revealing new routes to targeted therapies for patients with relapsed and metastatic disease (mSGC).

Methods

DNA was extracted from 40 µm of FFPE sections for 300 consecutive mSGC. CGP was performed on hybridization-captured, adaptor ligation-based libraries (mean coverage depth >500X) for up to 315 cancer-related genes. Total mutational burden (TMB) was determined on 1.2 Mbp of sequenced DNA. CRGA were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials.

Results

Adenoid Cystic Carcinoma (ACC) Acinic Cell Carcinoma (AciCC) Muco-epidermoid Carcinoma (MEC) Ductal Carcinoma (DCA) Adeno-Carcinoma NOS (AC-NOS) Carcinoma NOS (CA-NOS) Carcinoma ex Pleomorphic Adenoma (CPA)
Patients 28 73 48 41 54 32 24
GA/tumor 1.6 2.7 4.0 3.6 3.8 5.2 3.0
Significant GA MYB-NFIB FGFR1 CDK4 PTEN BRAF PIK3CA ERBB2 BRCA2 ERBB2 RET NF1 BRAF ERBB2 BRAF RET ERBB2 NF1 ERBB2
Mutation Frequencies
TP53 4% 8% 42% 54% 53% 59% 46%
ERBB2 0 0 8% 27% 13% 19% 29%
RET 0 0 0 5% 2% 0 0
ETV-NTRK Fusion 0 4% 2% 0 7% 0 0
BRAF 0 3% 2% 5% 6% 0 0
Tumor Mutation Burden (TMB) >10 mut/Mb 1% 3% 10% 11% 6% 13% 12%
Opportunity for Targeted Therapies Low Low Modest High High High High

Specialized mSGC (ACCand AciCC) have significantly fewer GA and targetable GA, as well as less TMB than non-specialized carcinomas (MEC, DCA, AC-NOS, CA-NOS, and CPA). Non-specialized CA are frequently ERBB2 driven, but also harbor GA in RET, BRAF and NF1. Clinical outcomes to targeted therapies for mSGC will be presented. Mammary associated secretory carcinomas (MASC) are grouped with AC-NOS; AciCC and MEC with ETV-NTRK fusions are likely MASC with unusual histologic presentations.

Conclusions

mSGC include specialized carcinomas (ACC and AciCC) with low GA frequencies, low TMB and limited opportunities for targeted therapies. The non-specialized group, however, features more GA, more targeted therapy opportunities for HER2, RET, BRAF and MTOR inhibitors, and higher TMB guiding the use of immune checkpoint inhibitors.

Clinical trial identification

Legal entity responsible for the study

Foundation Medicine, Inc.

Funding

Foundation Medicine

Disclosure

L.M. Gay: Employee of and has stock ownership in Foundation Medicine, Inc. J.S. Ross: Employee and stock holder of Foundation Medicine, Inc. K. Wang: Consultant for and stock owner of Foundation Medicine. J-A. Vergilio, J. Suh, S. Ramkissoon, S. Ali, V. Miller, P. Stephens, J.A. Elvin: Employee and stock owner of Foundation Medicine, Inc. All other authors have declared no conflicts of interest.

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