{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:47:19Z","timestamp":1789577239286,"version":"build-2803163510"},"reference-count":23,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"12","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,4,20]]},"abstract":"\n PURPOSE<\/jats:title>\n There is no standard second-line therapy for gastroenteropancreatic (GEP) and lung large-cell neuroendocrine carcinoma (NEC) after the failure of platinum-based chemotherapy. This study aimed to investigate the efficacy of nivolumab \u00b1 ipilimumab.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n The GCO-001-NIPINEC (ClinicalTrials.gov identifier:\n NCT03591731<\/jats:ext-link>\n ) trial was a noncomparative, open-label, phase II trial. The main inclusion criteria were age \u226518 years, performance status (PS) \u22642, advanced large- and small-cell GEP-NEC and large-cell lung NEC, and second- or third-line treatment for NECs refractory to platinum-based chemotherapy. Patients were randomly assigned (1:1) and stratified by age and PS to receive nivolumab (3 mg\/kg\/once every 2 weeks) \u00b1 ipilimumab (1 mg\/kg\/once every 6 weeks) for 2 years or until progression or unacceptable toxicity. The primary end point was objective response rate (ORR) at 8 weeks, assessed by investigators.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n A total of 185 patients (91 in the nivolumab arm and 94 in the nivolumab-ipilimumab arm) were enrolled between December 2018 and March 2021; 169 were analyzed (median age of 64.5 years, 71% male, 91% PS 0-1). The main primary tumor locations were lungs (50%), colorectal (15%), gastroesophageal (14%), and pancreatic (13%) regions. The ORR at 8 weeks was 7.2% (95% CI, 2.7 to 15.1]) in the nivolumab arm and 14.0% (95% CI, 7.4 to 23.1) in the nivolumab-ipilimumab arm. The best ORR was 9.6% and 20.9%, respectively, whereas the median progression-free and overall survival were approximately 2 months and 6 months in both arms. One treatment-related death occurred, in the nivolumab arm. The grade 3-4 adverse events (\u22655%) were asthenia (13%), gamma-glutamyl transferase increase (10%), alkaline phosphatase increase (9%), dyspnea (7%), and anemia (6%) in the nivolumab-ipilimumab arm.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n Nivolumab-ipilimumab could be a second-\/third-line treatment option for patients with NECs. However, given the limited magnitude of benefit, studies are warranted to evaluate its use earlier and\/or associated with chemotherapy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/jco-25-01657","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T20:59:28Z","timestamp":1772571568000},"page":"1120-1129","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Nivolumab \u00b1 Ipilimumab in Patients With Pretreated Advanced Neuroendocrine Carcinoma: The GCO-001 NIPINEC Randomized Phase II Trial"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4199-4561","authenticated-orcid":true,"given":"Thomas Pierre","family":"Walter","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Hospices Civils de Lyon, Lyon, France; Gastroenterology and technologies for Health, Research Unit INSERM UMR 1052 CNRS UMR 5286, Cancer Research Center of Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5921-7613","authenticated-orcid":true,"given":"Julien","family":"Mazieres","sequence":"additional","affiliation":[{"name":"Pulmonology Department, Toulouse University Hospital, Universit\u00e9 Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiane","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Centre Antoine-Lacassagne, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Lena","sequence":"additional","affiliation":[{"name":"Pneumology Department, Centre Hospitalier Universitaire Rennes, Universit\u00e9 Rennes 1, INSERM, UMR_S 1242, Centre Eugene Marquis, Rennes, 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of Hospices Civils de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7953-2533","authenticated-orcid":true,"given":"Thomas","family":"Egenod","sequence":"additional","affiliation":[{"name":"Pneumology Department, Limoges University Hospital, Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farid","family":"El Hajbi","sequence":"additional","affiliation":[{"name":"Oncology Department, Oscar Lambret Centre, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3981-6640","authenticated-orcid":true,"given":"Aur\u00e9lie","family":"Ferru","sequence":"additional","affiliation":[{"name":"Department of Abdominal Oncology, University Hospital of Poitiers, Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Cl\u00e9ment-Duchene","sequence":"additional","affiliation":[{"name":"Department of 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