{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:54:53Z","timestamp":1789584893398,"version":"build-2803163510"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014382","name":"Ipsen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014382","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In advanced neuroendocrine tumors (NET), antiproliferative treatment options beyond somatostatin analogs remain limited. Temozolomide (TMZ) has shown efficacy in NET alone or combined with other drugs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>SONNET (NCT02231762) was an open, multicenter, prospective, phase II study to evaluate lanreotide autogel 120 mg (LAN) plus TMZ in patients with progressive advanced\/metastatic grade 1\/2 gastroenteropancreatic (GEP) NET or of unknown primary. Patients could be enrolled at first-line or higher therapy line. The primary endpoint was disease control rate ([DCR], rate of stable disease [SD], partial [PR], and complete response [CR]) at 6 months of LAN and TMZ. Patients with nonfunctioning (NF) NET without progression at 6 months were randomized to 6-month LAN maintenance or watch and wait, patients with functioning (F)-NET with clinical benefit (PR, SD) continued on LAN.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Fifty-seven patients were recruited. The majority of patients received the study drug at second or higher treatment line and had an NET G2. DCR at 6 months LAN and TMZ was 73.5%. After 6 months of further LAN maintenance, 54.5% of patients with F-NET and 71.4% with NF-NET had SD or PR vs 41.7% with NF-NET on observation only. LAN and TMZ were effective in all subgroups analyzed. At 12 months of follow-up, median progression-free survival was 11.1 months. Median serum chromogranin A decreased except in NF-NET on observation. O6-methylguanine DNA methyltransferase promoter methylation appeared to better reflect TMZ response than loss of gene expression. During combination therapy, the most frequent treatment-emergent adverse events grade 3\/4 reported were nausea (14%), thrombocytopenia (12.3%), and neutropenia (8.8%). Four deaths were reported resulting from severe adverse events not considered related to study medication.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>LAN plus TMZ is a treatment option for patients with progressive GEP-NET with more aggressive biological profile showing a manageable safety profile.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyad325","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T17:47:56Z","timestamp":1704995276000},"page":"e643-e654","source":"Crossref","is-referenced-by-count":10,"title":["Combined Lanreotide Autogel and Temozolomide Treatment of Progressive Pancreatic and Intestinal Neuroendocrine Tumors: The Phase II SONNET Study"],"prefix":"10.1093","volume":"29","author":[{"given":"Marianne","family":"Pavel","sequence":"first","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH) , Berlin , Germany"},{"name":"Department of Medicine 1, Friedrich Alexander University Erlangen-Nuernberg, University Hospital Erlangen , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Lahner","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, University Hospital Essen , Essen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-4337","authenticated-orcid":false,"given":"Dieter","family":"H\u00f6rsch","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Endocrinology, Zentralklinik Bad Berka , Bad Berka , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8156-2915","authenticated-orcid":false,"given":"Anja","family":"Rinke","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital Gie\u00dfen and Marburg, Marburg and Philipps University Marburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-3208","authenticated-orcid":false,"given":"Timm","family":"Denecke","sequence":"additional","affiliation":[{"name":"Department of Radiology, Campus Virchow-Klinikum, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , Berlin , Germany"},{"name":"Department of Diagnostic and Interventional Radiology, University Medical Center Leipzig , Leipzig , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8589-4688","authenticated-orcid":false,"given":"Arend","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH) , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Regnault","sequence":"additional","affiliation":[{"name":"Ipsen Pharma , Boulogne-Billancourt , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorit","family":"Helbig","sequence":"additional","affiliation":[{"name":"Ipsen Pharma GmbH , M\u00fcnchen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Hoffmanns","sequence":"additional","affiliation":[{"name":"Ipsen Pharma GmbH , M\u00fcnchen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3248-5802","authenticated-orcid":false,"given":"Markus","family":"Raderer","sequence":"additional","affiliation":[{"name":"Medical University Vienna, Internal Medicine I, Division of Oncology , Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"2024050313101830500_CIT0001","first-page":"1335","article-title":"Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States","volume-title":"JAMA Oncol","author":"Dasari","year":"2017"},{"key":"2024050313101830500_CIT0002","first-page":"61","article-title":"Gastroenteropancreatic neuroendocrine tumours","volume-title":"Lancet Oncol","author":"Modlin","year":"2008"},{"key":"2024050313101830500_CIT0003","first-page":"vii72","article-title":"Gastrointestinal neuroendocrine 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