Endocrine Abstracts

Immunotherapy in neuroendocrine neoplasms (NENs) has been investigating over the years, mainly with interferon-alpha-2b and oncolytic virus, without conclusive results. The new immune checkpoint inhibitors (IC-Is) are in an initial phase of investigation in NENs with no published study so far, apart from Merkel Cell Carcinoma (MCC). For this latter NEN Avelumab has been recently approved by the FDA and EMA in advanced disease irrespective of the line of treatment. From a biological standpoint low grade neuroendocrine tumors (NETs) do not represent the ideal setting for investigating IC-Is as they have been reported to have a low tumor mutational burden (TMB); by contrast high grade neuroendocrine carcinomas (NECs), mainly small cell lung and extra-lung NECs are potentially more responsive. Preliminary results from some studies with anti-PD-1 agents were presented at the main congresses over the latest two years, including pembrolizumab, PDR001, and JS001.The tumor population was selected on the basis of positivity for PD-L1 just in the pembrolizumab study, that was a cohort of the Keynote 028 phase II basket trial. Unfortunately the three studies included a very heterogeneous population, in terms of primary sites, tumor grade and histotypes. Overall response rate (RR) was 6% in pancreatic NETs and 12% in extra-pancreatic NETs in the pembrolizumab trial, however the primary endpoint threshold of significance is unknown. The PDR001 trial was a negative study, due to the unmet primary endpoint of 10% RR in the global population, although a 20% of RR was observed in the lung cohort. The preliminary results of the JS001 study showed a high RR, especially in NETs compared with NECs and in PD-L1 positive compared with negative neoplasms. At the ASCO 2018 congress negative results of pembrolizumab in a population of NECs were reported. So far results of IC-Is in NETs are difficult to be interpreted, considering the heterogeneity of the tumor population included, the lack of a central pathology review and design of the trials. While the publication of the presented trials is waited then combinations of different new immunotherapeutic agents or IC-Is and molecular targeted agents should be investigated in homogeneous populations of NETs.