Abstract 961P
Background
Most personalized medicine studies in head and neck (HN) tumors focus on DNA alterations. There is limited data on the role of transcriptomics to guide treatment selection and its correlation with genomic data.
Methods
As part of the WINTHER trial, we performed targeted NGS (FoundationOne) on FFPE and gene expression profiling (customized Agilent assay on both tumor and analogous normal tissue) for DNA and RNA-matched drug ranks. Here we perform in-depth analysis of genomic and transcriptomic findings in a cohort of 29 pts with HN cancers.
Results
The HN cohort included 13 HNSCC, 9 adenoid cystic carcinoma (ACC) and 7 others (including 3 nasophagyngeal carcinoma (NPC)]. In total, 12 genomic- and 13 transcriptomic-matched therapies were identified. Based on genomic analysis, the proportion of targetable cases ranged from 77% in HNSCC, 55% in ACC and 28% in others, mostly PI3K pathway, receptor tyrosine kinase and DNA damage repair alterations. ACC had lower copy number alterations than others. TMB was low across all histologies, with the exception of one NPC (12 mut/Mb). There were few cases of oncogene amplifications, namely 2 cases with increased PIK3CA copy number in HNSCC (both with coexisting high PIK3CA expression in tumor and tumor/normal) and 1 HNSCC with FGFR2 amplification (without FGFR2 overexpression). On transcriptomic analysis, we found 7 cases with high expression of oncogenes in tumor samples, (>1.5 times the interquartile range above the third quartile). We identified high tumor expression of FGFR1 and/or FGFR2 in ACC (4/7 cases each) and HNSCC (1/11 each), all cases without coexisting genomic alterations in FGFR1 or FGFR2. In ACC, we found two-fold increase in mean number of potentially targetable alterations per sample with genomics + transcriptomics as compared to genomics (1.67 vs. 0.78). In other histologies, no significant changes in targetability rate were seen with transcriptomics added to genomics.
Conclusions
The pattern of genomic alteration differs by histology in HN cancer. The addition of transcriptomics to genomic analysis increases the targetability rate, especially in ACC, given high expression of FGFR1 and FGFR2, potential drivers that are often missed with genomic level analysis alone.
Clinical trial identification
NCT01856296.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The WINTHER study has received funding from the European Union Seventh Framework Program (FP7/2007–2013 under grant agreement no. 306125). The WINTHER study has been also partly funded by the ARC Foundation for Cancer Research (France), Pfizer Oncology, Lilly France SAS and Novartis Pharmaceuticals Corporation. This research has been partially funded by the Comprehensive Program of Cancer Immunotherapy and Immunology (CAIMI) supported by the Banco Bilbao Vizcaya Argentaria Foundation (BBVA Foundation) (grant 89/2017), La Caixa Foundation grant (LCF/PR/CEO7/50610001), and the Cellex Foundation providing research facilities and equipment. This work was also funded in part by The Fero/J.P. Morgan Private Bank Clinical Oncology Research Grant, the National Cancer Institute grant P30 P30-CA023100 (R.K.), the Israeli Science Foundation grant 1188/16 (E.R.), Instituto Salud Carlos III—Programa Rio Hortega Contract grant CM15/00255 (I.B.), the Canadian Institutes for Health Research (grant MOP-142281 to W.H.M.) and the Canadian Cancer Society (grant 703811 to W.H.M.).
Disclosure
I. Braña: Advisory/Consultancy, Research grant/Funding (self): Orion Pharma; Advisory/Consultancy, Research grant/Funding (self): Rakutan Pharma; Research grant/Funding (self), Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Merck Serono; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Research grant/Funding (self): Celgene; Research grant/Funding (self): Gliknik; Research grant/Funding (self): GSK; Research grant/Funding (self): Janssen; Research grant/Funding (self): KURA; Advisory/Consultancy, Research grant/Funding (self): MSD; Research grant/Funding (self): Novartis; Research grant/Funding (self): Pfizer; Advisory/Consultancy: Shattuck; Research grant/Funding (self): Northern Biologics; Research grant/Funding (self): Nanobiotics; Research grant/Funding (institution): Genentech Inc. E. Rubin: Advisory/Consultancy: Teva; Speaker Bureau/Expert testimony: Carmentix; Advisory/Consultancy: Hinoman; Speaker Bureau/Expert testimony: Equinom; Shareholder/Stockholder/Stock options: Carmentix. J. Rodon: Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Orion Pharmaceuticals; Advisory/Consultancy: Peptomyc; Advisory/Consultancy, Travel/Accommodation/Expenses: Kelun Pharmaceuticals/Klus Pharma; Advisory/Consultancy, Research grant/Funding (self): Spectrum Pharmaceuticals Inc.; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy: Roche Pharmaceuticals; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Certera; Advisory/Consultancy, Research grant/Funding (self): Bayer. W.H. Miller Jr: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen. A.M. Tsimberidou: Advisory/Consultancy: Roche; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Baxter; Research grant/Funding (institution): Foundation Medicine; Research grant/Funding (institution): ONYX; Research grant/Funding (institution): Bayer. F. Wunder: Full/Part-time employment: Worldwide Innovative Networking (WIN) Consortium. C. Bresson: Full/Part-time employment, Officer/Board of Directors: Worldwide Innovative Networking (WIN) Consortium. J. Tabernero: Advisory/Consultancy: Array Biopharma; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: BeiGene; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Chugai; Advisory/Consultancy: Genentech, Inc.; Advisory/Consultancy: Genmab A/S; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Imugene Limited; Advisory/Consultancy: Inflection Biosciences Limited; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Kura Oncology; Advisory/Consultancy: Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Menarini; Advisory/Consultancy: Roche Diagnostics; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Merus; Advisory/Consultancy: Molecular Partners; Advisory/Consultancy: Novartis; Advisory/Consultancy: Peptomyc; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Pharmacyclics; Advisory/Consultancy: ProteoDesign SL; Advisory/Consultancy: Rafael Pharmaceuticals; Advisory/Consultancy: F. Hoffmann-La Roche Ltd; Advisory/Consultancy: Sanofi; Advisory/Consultancy: SeaGen. V. Lazar: Full/Part-time employment, Officer/Board of Directors: Worldwide Innovative Networking (WIN) Consortium. R. Kurzrock: Officer/Board of Directors: Worldwide Innovative Networking (WIN) Consortium; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Sequenom; Research grant/Funding (institution): Foundation Medicine; Research grant/Funding (institution): Guardant Health; Research grant/Funding (institution): Grifols. All other authors have declared no conflicts of interest.