ABSTRACT
BACKGROUND: Pancreatic neuroendocrine tumors are rare neoplasms for which few predictive and/or prognostic biomarkers have been validated. Our previous work suggested the potential of the combined expression of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) as prognostic factors for relapse and survival. METHODS: In this new multicenter study we evaluated immunohistochemistry expression in 76 patients with advanced PanNET who were treated with capecitabine-temozolomide or everolimus. Based on the immunohistochemistry panel, an immunohistochemistry prognostic score (IPS) was developed. RESULTS: In patients treated with capecitabine and temozolomide, low IPS was an independent prognostic factor for progression-free-survival and overall-survival. Similar findings were observed with highest IPS for overall-survival in patients treated with everolimus. CONCLUSION: From our knowledge, it is the first time that a simple IPS could be useful to predict outcome for patients with metastatic pancreatic neuroendocrine tumors treated with everolimus or capecitabine and temozolomide.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Everolimus/therapeutic use , Immunohistochemistry/methods , Immunosuppressive Agents/therapeutic use , Neuroendocrine Tumors/drug therapy , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Cell Cycle Proteins/analysis , Cell Line, Tumor , DNA Modification Methylases/analysis , DNA Repair Enzymes/analysis , Female , Humans , Intracellular Signaling Peptides and Proteins/analysis , Male , Middle Aged , Neoplasm Recurrence, Local , Neuroendocrine Tumors/mortality , Nuclear Proteins/analysis , Pancreatic Neoplasms/mortality , Prognosis , Progression-Free Survival , Survival Analysis , Tumor Suppressor Proteins/analysis , Young AdultABSTRACT
Immunotherapy has radically transformed the management of metastatic malignant melanoma. Ipilimumab, a CTLA-4-targeted monoclonal antibody, was the first immunotherapeutic drug to reach a survival benefit compared with traditional chemotherapy. PD-1 targeted therapies, pembrolizumab and nivolumab, have demonstrated, in recent clinical trials, to be even more effective and safer. PD-1 and CTLA-4 blockade combination appears to improve the outcomes achieved so far, although increasing toxicity. However, many questions concerning the optimal timing of administration or the most adequate sequence of treatment are yet to be answered.
