Abstract 245P
Background
Neuroendocrine neoplasms (NENs) are rare cancers, accounting for approximately 0.5% of all newly diagnosed malignancies. Due to their rarity, the comprehensive understanding of their molecular profiles remains unclear. The aim of present study is to analyze the molecular profiles of NENs and their association with clinical characteristics.
Methods
We evaluated the whole-exome (WES) and -transcriptome sequencing (WTS) data from 37 patients (pts) with NENs enrolled in MONSTAR-SCREEN-2, a multi-institutional molecular profiling project (UMIN000043899). Genomic alterations in tumor tissue and blood samples were evaluated separately for neuroendocrine carcinomas (NEC) and neuroendocrine tumors (NET). Genomic alteration status from WES and RNA expression data from WTS were utilized to evaluate associations with progression-free survival (PFS) for primary treatment.
Results
Of 37 pts, 19/18 were classified as NEC/NET, respectively. In tissue genotyping, mutations in TP53 (89%), RB1 (47%), and KRAS (26%) were prevalently observed in NEC, whereas MEN1 (39%), ATM (22%), and MTOR (17%) in NET. In 25 patients with blood-based genotyping data available, pathogenic alterations were identified in 14 pts (74%) in NEC and 11 pts (61%) in NET, respectively. Mutations in TP53 (71%), RB1 (29%), and KRAS (29%) were prevalently observed in NEC, whereas ARIDA (27%) and KMT2D (18%) were prevalently detected in NET. Germline BRCA2 mutations were detected in 2 pts (1 in NEC and 1 in NET); however, no MEN1 mutations were identified. Clonal hematopoiesis was prevalently detected in TET2 (27%), DNMT3A (18%), and KMT2D (9%). In survival analyses for pts with NEC, no significant prognostic markers were identified in WTS data; pts with TP53 mutations showed a slight trend towards shorter PFS compared to pts without TP53 mutations (median PFS: 7.1 vs. 4.7 months Log-rank P=0.29) in WES data.
Conclusions
We conducted a comprehensive genotyping of tissue and blood samples from a limited number of pts with NENs. Further research with larger cohorts is warranted to elucidate the molecular profiles in more detail and potentially identify new therapeutic targets.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
SCRUM-Japan Funds.
Disclosure
Y. Matsubara: Financial Interests, Personal, Invited Speaker: Takeda, Taiho, MSD, Eli Lilly Japan K.K. S. Kadowaki: Financial Interests, Personal, Invited Speaker: Taiho, MSD, Ono, Daiichi Sankyo, BMS, Bayer, Merck, Eisai, Otsuka; Financial Interests, Institutional, Funding: Eli Lilly, MSD, Ono, Daiichi Sankyo, Chugai, Nobelpharma, Yansen, AstraZeneca. N. Okano: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Eli Lilly Japan, Eisai, Bayer Yakuhin, Chugai Pharma, Ono Pharmaceutical, Daiichi Sankyo, AstraZeneca, MSD, Incyte, Nihon Servier; Financial Interests, Personal, Funding: J-Pharma. M. Ueno: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Incyte, MSD, Nihon Servier, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, J-pharma, Eisai, Yakult Honsha; Financial Interests, Personal, Advisory Board: Nippon Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Local PI: Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, DFP, Daiichi Sankyo, Eisai, Incyte, MSD, Merck Biopharma, Ono Pharmaceutical, Taiho Pharmaceutical, Novartis, J-pharma, Novocure, Chiome Bioscience. A. Makiyama: Financial Interests, Personal, Invited Speaker: Eli Lilly, Taiho, Ono, Daiichi Sankyo, Bristol Myers Squibb. T. Esaki: Financial Interests, Personal, Invited Speaker: Chugai, Taiho, MI force, Daiichi Sankyo, Eli Lilly, Ono, Bristol; Financial Interests, Institutional, Local PI: MSD, Ono, Nihon Kayaku, IQVIA, Daiichi Sankyo, Chugai, Syneos Health Clinical, Quintiles, Astellas, Astellas Amgen Biopharma, Asahikasei Pharma, Amgen, ALX Oncology, Seagen, Taiho, Jazz Pharmaceuticals Ireland, Bristl. Y. Kagawa: Financial Interests, Personal, Invited Speaker: Bayer, Chugai, Ono, Lilly, Merck, Takeda, MSD; Financial Interests, Personal and Institutional, Coordinating PI: Ono. S. Boku: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb, MSD Japan, Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Asahi Kasei Pharma Co.; Financial Interests, Institutional, Funding: Kyo Diagnostics Co., Ltd. T. Fujisawa: Financial Interests, Personal, Invited Speaker: Amelieff Co Ltd. Y. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Guardant Health Pte Ltd, MSD K.K, Eisai, Zeria Pharmaceutical, Miyarisan pharmaceutical, CareNet, Inc., Hisamitsu Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo Co., Ltd., Becton Dickinson, Guardant Health Japan Corp.; Financial Interests, Personal, Advisory Board: Natera, Inc., Roche Ltd., Seagen, Inc., Premo Partners, Inc., Daiichi Sankyo Co., Ltd., Takeda, Exact Sciences, Gilead Sciences, Guardant Health Pte Ltd; Financial Interests, Institutional, Funding: Taiho, Chugai, Guardant Health, Genomedia, Daiichi Sankyo, Roche Diagnostics, Guardant Health AMEA, Inc., Tempus; Financial Interests, Institutional, Coordinating PI: Seagen. H. Bando: Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Other, Personal, Other, Lecture fee: Ono Pharmaceutical, Taiho pharmaceutical, Eli Lilly Japan. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd, Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., FALCO Biosystems Ltd., Merus N.V., Bristol Myers Squibb K.K., Medical & Biological Laboratories Co., LTD., Takeda Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.