Outcomes in high-grade neuroendocrine carcinomas (HG-NEC) of the gastrointestinal (GI) tract with modern therapies.

Abstract

e15609 Background: HG-NEC of the GI tract are rare and aggressive neoplasms with poor prognosis. Approximately 37.5% of extra-pulmonary NEC are of the GI origin and are most commonly located in esophagus, stomach, pancreas and colon (1,2). Median survival of 7.5 months, with range of 5.7 months to 25.1 months has been reported (2). However, data regarding response to immunotherapy, as well as response to molecularly directed therapies are sparse. In this study, we conducted a retrospective review of GI tract HG-NEC with objective to assess role of modern diagnostics and therapies in clinical outcomes. Methods: We identified 14 patients with GI tract HG-NEC who received care at University of Chicago Medical Center (UCMC). Electronic medical records were reviewed for disease stage, treatments and clinical course. We reviewed available next generation sequencing (NGS) and circulating tumor DNA (ct-DNA) test results. In this cohort, UCMC’s NGS panel: Oncoplus was available and Guardant 360 results were reviewed for liquid biopsy. Results: In our initial review, site of origin included right side of colon (46%), left sided colon (46%), and anus/anorectal (15%). Median overall survival (mOS) ranged from 1.3 months to 81.3 months, and notably the median response to chemo-immunotherapy (IO) was 7.9 months (table 1). Notably one patient received maintenance therapy with immunotherapy alone with progression of disease (POD) in 3 weeks. Six patients had NGS results of which three (50%) had therapeutic targetable alterations (Table). Two patients had liquid biopsy done, of which one had targetable alterations and the other had no tumor related alterations detected. Of the two patients with targetable lesions, one patient has received targeted therapy with POD in 1.2 months and median OS 8.8 months; the other is in the process of initiating targeted therapy. Conclusions: To our knowledge, this is the first report to show a response to combination chemo-immunotherapy and targeted therapies in HG-NEC of GI tract. We are collaborating with other institutions to collate outcomes to similar therapy approaches in this patient cohort. With our study, we hope to inform future therapies and innovation in this important disease.