{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:51:32Z","timestamp":1791244292927,"version":"4.1.0"},"reference-count":29,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,3,10]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              Alkylating agents (ALKY) are the main chemotherapies used for advanced neuroendocrine tumors (NETs). O\n              <jats:sup>6<\/jats:sup>\n              -Methylguanine-DNA methyltransferase (MGMT) status, as proficient (p) or deficient (d), may predict the response to ALKY.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>PATIENTS AND METHODS<\/jats:title>\n            <jats:p>\n              MGMT-NET (ClinicalTrials.gov identifier:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03217097\">NCT03217097<\/jats:ext-link>\n              ) was a phase II trial randomly assigning 1:1 for pMGMT or 2:1 for dMGMT-NETs to either ALKY or oxaliplatin (Ox). Inclusion criteria were a confirmed advanced pancreatic, thoracic, or unknown primary NETs with an indication for chemotherapy and tissue available. The primary aim was to detect a difference of 35% between the 3-month objective response rate (ORR) in pMGMT-NETs versus in dMGMT-NETs when treated with ALKY. A biomarker-stratified design was performed to compare ALKY and Ox in the dMGMT and pMGMT strata for the secondary end points. dMGMT was defined using pyrosequencing (PSQ; methylated\n              <jats:italic>MGMT<\/jats:italic>\n              \u22659%) and using immunochemistry (\n              <jats:italic>H<\/jats:italic>\n              -score of MGMT &lt;50) when PSQ was not interpretable.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              From October 2018 to October 2021, 105 patients (55 pancreas, 38 thorax, 12 unknown) started either ALKY (n = 62) or Ox (n = 43). The median age was 63 years (range, 30-84), and 59% were males. NETs were G1 (19%), G2 (69%), or G3 (10%). Among patients with interpretable MGMT status, 56.9% (58 of 102) had a dMGMT-NET. The primary end point was not reached; the 3-month ORR was 10 (29.4%) versus 2 (8%), and the odds ratio was 3.5 (0.58-21.16),\n              <jats:italic>P<\/jats:italic>\n              = .172. However, best ORR (18 [52.9%]\n              <jats:italic>v<\/jats:italic>\n              3 [11.5%]) and median progression-free survival (14.6 [95% CI, 7.2 to 22.1]\n              <jats:italic>v<\/jats:italic>\n              11.3 [9.4 to 13.2] months) were higher for dMGMT-NETs versus pMGMT-NETs. MGMT status does not seem to affect the Ox efficacy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>Despite the fact that the primary end point was not reached, ALKY has clinical activity in patients with dMGMT-NETs.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/jco.23.02724","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T20:59:25Z","timestamp":1732568365000},"page":"960-971","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":23,"title":["Oxaliplatin-Based Versus Alkylating Agent in Neuroendocrine Tumors According to the O\n            <sup>6<\/sup>\n            -Methylguanine-DNA Methyltransferase Status: A Randomized Phase II Study (MGMT-NET)"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct03217097","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4199-4561","authenticated-orcid":true,"given":"Thomas","family":"Walter","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France"},{"name":"Gastroenterology and Technologies for Health, INSERM UMR 1052 CNRS UMR 5286, Cancer Research Center of Lyon, University of Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5093-0212","authenticated-orcid":true,"given":"Thierry","family":"Lecomte","sequence":"additional","affiliation":[{"name":"Department of Hepatogastroenterology and Digestive Oncology, Tours University Hospital, Tours, France"},{"name":"Inserm UMR 1069, Nutrition, Croissance et Cancer, University of Tours, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1276-3289","authenticated-orcid":true,"given":"Julien","family":"Hadoux","sequence":"additional","affiliation":[{"name":"Departement of Endocrine Oncology, Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Niccoli","sequence":"additional","affiliation":[{"name":"Oncology Department, Institut Paoli Calmette, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6375-2839","authenticated-orcid":true,"given":"L\u00e9a","family":"Saban-Roche","sequence":"additional","affiliation":[{"name":"Oncology Department, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5684-1106","authenticated-orcid":true,"given":"Elisabeth","family":"Gaye","sequence":"additional","affiliation":[{"name":"Oncology Department, Oscar Lambret, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8344-1762","authenticated-orcid":true,"given":"Rosine","family":"Guimbaud","sequence":"additional","affiliation":[{"name":"Department of Digestive Medical Oncology, CHU de Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Baconnier","sequence":"additional","affiliation":[{"name":"Departement of Hepato-gastroenterology and Digestive Oncology, Annecy Hospital, Annecy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2735-6448","authenticated-orcid":true,"given":"Vincent","family":"Hautefeuille","sequence":"additional","affiliation":[{"name":"Departement of Hepato-gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-0149","authenticated-orcid":true,"given":"Christine","family":"Do Cao","sequence":"additional","affiliation":[{"name":"CHU Lille, Department of Endocrinology, Diabetology, and Metabolism, University Hospital of Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Petorin","sequence":"additional","affiliation":[{"name":"Oncology Department, Estaing Hospital, Clermont-Ferrand, 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