Riesco-Martinez, Maria CarmenCapdevila, JaumeAlonso, VicenteJimenez-Fonseca, PaulaTeule, AlexGrande, EnriqueSevilla, IsabelBenavent, MartaAlonso-Gordoa, TeresaCustodio, AnaAnton-Pascual, BeatrizHernando, JorgePolo, EduardoCastillo-Trujillo, Oscar AlfredoLamas-Paz, ArantzaTeijo, AnaRodriguez-Gil, YolandaSoldevilla, BeatrizGarcia-Carbonero, Rocio2026-01-282026-01-282024-12Riesco-Martinez, M C, Capdevila, J, Alonso, V, Jimenez-Fonseca, P, Teule, A, Grande, E, Sevilla, I, Benavent, M, Alonso-Gordoa, T, Custodio, A, Anton-Pascual, B, Hernando, J, Polo, E, Castillo-Trujillo, O A, Lamas-Paz, A, Teijo, A, Rodriguez-Gil, Y, Soldevilla, B & Garcia-Carbonero, R 2024, 'Nivolumab plus platinum-doublet chemotherapy in treatment-naive patients with advanced grade 3 Neuroendocrine Neoplasms of gastroenteropancreatic or unknown origin : The multicenter phase 2 NICE-NEC trial (GETNE-T1913)', Nature Communications, vol. 15, no. 1, 6753. https://doi.org/10.1038/s41467-024-50969-82041-1723PubMedCentral: PMC11310219https://hdl.handle.net/10641/7673Publisher Copyright: © The Author(s) 2024.The prognosis of patients with advanced high-grade (G3) digestive neuroendocrine neoplasms (NENs) is rather poor. The addition of immune checkpoint inhibition to platinum-based chemotherapy may improve survival. NICE-NEC (NCT03980925) is a single-arm, phase II trial that recruited chemotherapy-naive, unresectable advanced or metastatic G3 NENs of gastroenteropancreatic (GEP) or unknown origin. Patients received nivolumab 360 mg intravenously (iv) on day 1, carboplatin AUC 5 iv on day 1, and etoposide 100 mg/m2/d iv on days 1–3, every 3 weeks for up to six cycles, followed by nivolumab 480 mg every 4 weeks for up to 24 months, disease progression, death or unacceptable toxicity. The primary endpoint was the 12-month overall survival (OS) rate (H0 50%, H1 72%, β 80%, α 5%). Secondary endpoints were objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and safety. From 2019 to 2021, 37 patients were enrolled. The most common primary sites were the pancreas (37.8%), stomach (16.2%) and colon (10.8%). Twenty-five patients (67.6%) were poorly differentiated carcinomas (NECs) and/or had a Ki67 index >55%. The ORR was 56.8%. Median PFS was 5.7 months (95%CI: 5.1-9) and median OS 13.9 months (95%CI: 8.3-Not reached), with a 12-month OS rate of 54.1% (95%CI: 40.2-72.8) that did not meet the primary endpoint. However, 37.6% of patients were long-term survivors (>2 years). The safety profile was consistent with previous reports. There was one treatment-related death. Nivolumab plus platinum-based chemotherapy was associated with prolonged survival in over one-third of chemonaïve patients with G3 GEP-NENs, with a manageable safety profile.1292779enghttp://creativecommons.org/licenses/by-nc-nd/4.0/General ChemistryGeneral Biochemistry, Genetics and Molecular BiologyGeneral Physics and AstronomyYesyesjournal articleopen access10.1038/s41467-024-50969-8https://www.scopus.com/pages/publications/85200914045https://www.scopus.com/pages/publications/85200914045#tab=citedBy