Annals of Oncology 27 (Supplement 6): vi328–vi350, 2016 doi:10.1093/annonc/mdw376.4
head and neck cancer 954O
Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies
L.M. Gay1, J.S. Ross2, K. Wang3, J-A. Vergilio1, J. Suh1, S. Ramkissoon1, D. Bowles4, H. Serracino4, J. Russell5, S. Ali6, V. Miller6, P. Stephens7, J.A. Elvin1 1 Pathology, Foundation Medicine, Inc., Cambridge, MA, USA, 2Pathology, Albany Medical Center, Albany, NY, USA, 3Genetics, Zhejiang Cancer Hospital, Hangzhou, China, 4Division of Medical Oncology, University of Colorado Denver, Denver, CO, USA, 5Medical Oncology, Moffitt Cancer Center, Tampa, FL, USA, 6 Clinical Development, Foundation Medicine, Inc., Cambridge, MA, USA, 7Clinical Genomics, Foundation Medicine, Inc., Cambridge, MA, USA 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: 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. 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.
Table: 954O
abstracts
Adenoid Cystic Carcinoma (ACC) Patients GA/tumor Significant GA Mutation Frequencies TP53 ERBB2 RET ETV-NTRK Fusion BRAF Tumor Mutation Burden (TMB) >10 mut/Mb Opportunity for Targeted Therapies
Acinic Cell Carcinoma (AciCC)
Muco-epidermoid Carcinoma (MEC)
Ductal Carcinoma (DCA)
Adeno-Carcinoma NOS (AC-NOS)
Carcinoma NOS Carcinoma ex (CA-NOS) Pleomorphic Adenoma (CPA)
28 73 1.6 2.7 MYB-NFIB FGFR1 CDK4 PTEN BRAF
48 4.0 PIK3CA ERBB2 BRCA2
41 3.6 ERBB2 RET NF1 BRAF
54 3.8 ERBB2 BRAF RET
32 5.2 ERBB2 NF1
24 3.0 ERBB2
4% 0 0 0 0 1%
8% 0 0 4% 3% 3%
42% 8% 0 2% 2% 10%
54% 27% 5% 0 5% 11%
53% 13% 2% 7% 6% 6%
59% 19% 0 0 0 13%
46% 29% 0 0 0 12%
Low
Low
Modest
High
High
High
High
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