660MO - Molecular targets in salivary gland cancers: A comprehensive genomic analysis of 1,666 cases

Background

Next Generation Sequencing (NGS) to identify key molecular targets is an important aspect of management in advanced Salivary Gland Carcinomas (SGC).

Methods

DNA was extracted from tissues of advanced SGC and Comprehensive Genomic Profiling (CGP) was done to evaluate for base substitutions, short insertions, deletions, copy number changes, gene fusions and rearrangements. Tumor Mutation Burden (TMB) was calculated on up to 1.25 Mb.

Results

The table shows the descriptive analysis of 1,666 SGC with clinically relevant Genomic Alterations (GA). Adenoid Cystic Carcinoma (ACC) (28.3%) was the commonest subtype. CDKN2A and CDKN2B GA were common in Acinic cell carcinoma (AcCC) (59 and 37.4%) and mucoepidermoid carcinoma (MEC) (52.5 and 30.5%). PIK3CA was common in Ductal Ca (32.6%) and High-grade Ca NOS (21.3%), making agents like Alpelisib, a consideration. ERBB2 amplification/Short Variants (amp/SV) were frequent in Carcinoma ex Pleomorphic Adenoma (Ca ex PA) (17.6/9.8%) and Ductal Ca (16.3/3.6%). ERBB2 directed therapies can play a crucial role in their management. BRAF GA was common in Ductal Ca (5.6%) and ACC (3.6%). Targets including RET, FGFR, NTRK, BRCA and EGFR had a low incidence. TMB >10 was common in High-grade NOS (18.3%) and MEC (16.9%). High PDL1 was also common in High grade NOS (8.9%) making us believe that this subtype may have the best response to immunotherapy (IO). Table: 660MO

Conclusions

This large dataset reveals many opportunities for IO and targeted therapy contributing to the continuing increased precision in the selection of treatment for these patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Foundation Medicine Inc.

Disclosure

A. Sivapiragasam: Financial Interests, Personal, Advisory Role: Pfizer, Puma Oncology, Blueprint Medicines, Immunomedics. N.A. Danziger: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffman La-Roche LTd. J.S. Ross: Financial Interests, Personal, Full or part-time Employment, Medical Director: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche Holdings, Tango Therapeutics, Celsius Therapeutics. All other authors have declared no conflicts of interest.