1159P - Molecular characterization of extra-pulmonary mixed adeno-neuroendocrine carcinomas: The NIRVANA substudy

Background

Extra-pulmonary (EP) mixed neuroendocrine/non-neuroendocrine carcinomas (MiNENs) are heterogeneous and rare neoplasms with dismal prognosis. The gene mutation profiles are incompletely understood. Therefore, the purpose of this study is to retrospectively characterize the clinical and molecular features of EP MiNENs consecutive assessed at European Institute of Oncology (Milan).

Methods

Surgical/biopsies specimens of advanced MiNENs were examined by clinical and morphological features review. All tumor samples were also evaluated by immunohistochemistry (IHC) for microsatellite instability (MSI) analyses and a 26-gene panel by next-generation sequencing (NGS) using a targeted multi-genes panel.

Results

Between 2015-2023, 16 MiNENs out of 80 cases of high grade neuroendocrine neoplasms (NENs) were examinated. They mostly presented large-cell features in the NEC-component (77%) and adenocarcinoma histotype in the non-NEC component (85%). More than half of the population had colo-rectal (CR) as primary site, mainly right side. The most represented mutations were TP53 (9%) and KRAS (20%) mostly in right-sided neoplasms as in pure adenocarcinomas. MSI was seen in 1 patient. Other mutated genes were detected in less than 10 cases. A total of 14/16 (87%) patients received at least one line of chemotherapy, typically carbo-platinum-based regimens with 50% disease control rate (DCR). Among them, 11 patients (70%) received a second-line therapy, mainly irinotecan-containing without benefit.

Conclusions

Our study seems to show that a subset of EP MiNENs exhibit potentially druggable oncological drivers which could benefit from matched therapies and improve outcomes as in other tumor types.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Istituto Europeo di Oncologia (IEO), IRCCS.

Funding

Spontaneous donation of patients.

Disclosure

F. Spada: Financial Interests, Personal, Invited Speaker: Advanced Accelerator Applications, SAS SPA; Financial Interests, Personal, Writing Engagement: Ipsen, Merck, Advanced Accelerator Applications; Non-Financial Interests, Project Lead, Coordinator of neuroendocrine neoplasms guidelines: AIOM (Italian Association Of Medical Oncology); Non-Financial Interests, Leadership Role, I am member of Scientific Board and lead of neuroendocrine Neoplasms Guidelines: ITANET (Italian Association Of Medical Oncology). N. Fazio: Financial Interests, Personal, Other, Steering committee: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Merck, MSD, Novartis, Ipsen; Financial Interests, Institutional, Local Pi: Astellas, Msd, Beigene, Nucana, Ipsen, Fibrogen, Itm, Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Ipsen, Novartis, Merck; Non-Financial Interests, Other, Steering committee: SPARC Europe; Non-Financial Interests, Member of Board of Directors: ENETS; Non-Financial Interests, Other, Member of the NET Faculty: ESMO; Non-Financial Interests, Other, Internal reviewer of NET guidelines: AIOM. All other authors have declared no conflicts of interest.