Abstract 87P
Background
HG-NEN is a heterogeneous group of rare cancers, including neuroendocrine carcinoma (NEC) and high-grade neuroendocrine tumors (NET G3). HG-NENs are characterized by poor differentiation, rapid growth, limited treatment options and poor prognosis. The aim of this study was to investigate the potential of WES/WGS to inform treatment of metastatic HG-NEN.
Methods
Blood and tumor biopsies from 49 patients (pts) with HG-NEN referred to the phase 1 Unit at Department of Oncology, Copenhagen University Hospital – Rigshospitalet, Denmark were analyzed with WES (n=30) or WGS (n=19) in the framework of the CoPPO project in the period 2013- 2022. Tumor mutational burden (TMB) was calculated as number of non-synonymous mutations per mega base (Mb).
Results
45 pts had somatic mutations in 61 selected different cancer associated genes. Most frequent somatic mutations included TP53 (33/49), APC (13/49), KRAS (9/49), BRAF (9/49), and RB1 (8/49). When compared, NET G3 (n=11) and NEC (n=38) appeared as molecularly distinct i.e., only one NET G3 was TP53 mutated compared to 33 NEC. Overall, the NET G3 contained fewer oncogenic mutations (median=1) compared to NEC (median=4). We identified 29 pts (59%) with actionable genomic variants (most frequently BRAF V600E, n=7 and TMB-high defined as >10 mutations per Mb n=24).
Conclusions
Extensive genomic profiling in pts with HG-NEN holds potential as more than half of the pts presented with potential treatment targets extending therapeutic options.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
I.K. Buhl: Financial Interests, Personal, Full or part-time Employment: Aida Oncology Aps (shares). M. Hoejgaard: Financial Interests, Personal, Other, Advisory role for various diagnostic companies/investors: LingoMedical; Financial Interests, Personal, Stocks/Shares, Stocks, I. Spanggaard: Financial Interests, Institutional, Invited Speaker: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer; Non-Financial Interests, Personal, Principal Investigator: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer. K.S. Rohrberg: Financial Interests, Personal, Invited Speaker: Bayer, Amgen, MSD, GSK; Financial Interests, Personal, Advisory Board: AbbVie, Genmab; Financial Interests, Institutional, Invited Speaker, Compensation for conduction of clinical trial: Lilly, Roche/Genentech, Bristol Myers Squibb, Symphogen, Pfizer, Novartis, Alligator Bioscience, Genmab, BioInvent, Monta Bioscience, Amgen, Navire; Financial Interests, Institutional, Other, Compensation for conduction of clinical trial: Bayer, Incyte, Puma Biotechnology, Orion Clinical. All other authors have declared no conflicts of interest.