{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:54:54Z","timestamp":1789584894902,"version":"build-2803163510"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eli Lilly"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Well-differentiated neuroendocrine tumors (NET) are highly vascular tumors characterized by their expression of vascular endothelial growth factor (VEGF). This trial investigated the activity of ramucirumab, a monoclonal antibody that targets VEGF receptor-2 (VEGFR-2) and inhibits activity of VEGF, in combination with somatostatin analog therapy in patients (pts) with advanced extra-pancreatic NET.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a single-arm phase II trial enrolling pts with advanced, progressive extra-pancreatic NET. Patients were treated with ramucirumab 8\u00a0mg\/kg intravenously on days 1 and 15 of each 28-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints toxicity, radiographic and biochemical tumor response rate, and overall survival (OS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The trial enrolled 43 patients. Primary tumor sites included small intestine 20 (46%), lung 10 (23%), thymus 3 (7%), rectum 1(2%), kidney 1(2%), and unknown primary 8(18%). Median PFS was 14.2 months (95% CI, 9.0-25.6 months), and median OS was 24.9 months (95% CI, 20.7-43.1 months). Best response by RECIST 1.1: partial response 5% (95% CI, 0.6%-15.8%). Chromogranin A levels dropped by at least 50% in 10% of the 37 patients who had elevated levels at baseline. Most common all-grade adverse events included fatigue (84%) and hypertension (84%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Ramucirumab demonstrated efficacy and safety in this single-arm phase II trial. These findings support the continued evaluation of angiogenesis inhibitors in the treatment of NET.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical trial registration<\/jats:title>\n                  <jats:p>NCT02795858.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyae364","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T06:02:07Z","timestamp":1737439327000},"source":"Crossref","is-referenced-by-count":4,"title":["A phase II study of ramucirumab and somatostatin analog therapy in patients with advanced neuroendocrine tumors"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5745-2994","authenticated-orcid":false,"given":"Kimberly","family":"Perez","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA\u00a002215 ,","place":["United States"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew H","family":"Kulke","sequence":"additional","affiliation":[{"name":"Section of Hematology and Oncology, Boston University and Boston Medical Center , Boston, MA 02118 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zheng","sequence":"additional","affiliation":[{"name":"Biostatistics Center, Massachusetts General Hospital , Boston, MA 02114 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Allen","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["United States"]},{"name":"Department of Medicine, Massachusetts General Hospital , Boston, MA 02114 ,","place":["United 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Medicine, Massachusetts General Hospital , Boston, MA 02114 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA\u00a002215 ,","place":["United States"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Rubinson","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA\u00a002215 ,","place":["United States"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B","family":"Yurgelun","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA\u00a002215 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