Abstract 957P
Background
HNAMB is an extremely uncommon HN malignancy with unique clinical presentations, histology and clinical course. We performed a comprehensive genomic profiling (CGP) study of HNAMB to learn of potential genomic alterations (GA) linked to targeted and immune checkpoint inhibitor (ICPI) therapies.
Methods
14 HNAMB FFPE tissues were sequenced using a hybrid-capture based CGP method to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3).
Results
ll patients in our cohort had clinically advanced unresectable or metastatic disease. There were 8 (57%) male and 6 (43%) female patients in this study with a median age of 62 years (range 24 to 86 years). The original primary HN tumor was used for sequencing in 7 (50%) cases and a metastasis biopsy was used in 7 cases (50%) including 6 lung and 1 mediastinal metastatic sites. There were 4.7 GA/tumor with 82% short variant (SV) GA, 16% copy number (CN) GA and 2% rearrangements. Noteworthy potentially targetable GA included 6 (42%) HNAMB with activating BRAF mutations (all V600E), 5 (36%) PIK3CA (4 SV and 1 CN), 4 (29%) FGFR2 (4 SV), 1 (7%) EGFR (1 CN) and 1 (7%) ROS1 (1 rearrangement). The ROS1 rearrangement involved intron 33 and is of uncertain significance with respect to oncogenesis and response to anti-ROS1 tyrosine kinase inhibitors (TKIs). SMO GA were identified in 5 cases (SV, 36%). All (100%) of cases were MSI stable and featured a median TMB of 2.5 mutations/Mb with no (0%) cases having a TMB > 6 mutations/Mb. Four cases underwent PD-L1 IHC staining and 3 (75%) featured low positive (1-49%) staining and 0 (0%) had high IHC staining.
Conclusions
This CGP study reproduced the finding of a high frequency of BRAF V6600E mutations in HNAMB, and identified additional potentially targetable kinase mutations in PIK3CA, FGFR2 and EGFR as well as a possible targetable ROS1 rearrangement. Further study of HNAMB targeted therapies in the setting of rare cancer clinical trials appears warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Foundation Medicine Inc.
Funding
Foundation Medicine Inc.
Disclosure
P. Reddy: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. N.A. Danziger, J.K. Killian, D.I. Lin, E. Williams, A. Hemmerich, D. Duncan, C. Edgerly, M. Hiemenz: Full/Part-time employment: Foundation Medicine Inc. J. Elvin, J-A. Vergilio, S. Ramkissoon, E. Severson, J.H. Chung, K. McGregor, A.B. Schrock: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. R. Huang: Full/Part-time employment: Foundation Medicine Inc.; Full/Part-time employment, patents: Roche Ltd. J. Venstrom: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc.; Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech. B. Alexander: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc.; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Puma. J.S. Ross: Leadership role, Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc.; Advisory/Consultancy: Celsius Therapeutics.