{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:39:12Z","timestamp":1789558752199,"version":"build-2803163510"},"reference-count":46,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"29","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,10,10]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>Patients with advanced, well-differentiated extrapancreatic neuroendocrine tumors (epNETs) have limited systemic treatment options. Pazopanib, an oral multikinase inhibitor with activity against vascular endothelial growth factor receptor (VEGFR)-2 and -3, PDGFR-alpha and-beta, and c-Kit, was tested for efficacy in epNET.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>PATIENTS AND METHODS<\/jats:title>\n            <jats:p>We conducted a multicenter, randomized, double-blind, phase II study of pazopanib (800 mg once daily) versus placebo in low- to intermediate-grade epNET with radiologic progressive disease (PD) within 12 months of study entry. Previous somatostatin analog (SSA) was required for midgut tumors, and concurrent SSA was allowed. The primary end point was progression-free survival (PFS) by blinded independent central review. Unblinding and crossover were allowed if PD was confirmed by central review.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              One hundred seventy-one patients (97 pazopanib and 74 placebo) were randomly assigned between September 2013 and October 2015. The majority had a midgut primary site (75%) and previous SSA treatment (93%). About half (49%) of the patients had functional tumors. The median follow-up was 61 months (95% CI, 60 to 63). Median PFS was 11.8 versus 7.6 months in pazopanib versus placebo, respectively (hazard ratio, 0.54 [95% CI, 0.37 to 0.79];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt; .001); 49 placebo patients crossed over to pazopanib. There was no significant difference in overall survival between the treatment arms. Rates of grade 3 or greater adverse events (regardless of attribution) were higher in pazopanib versus placebo (84%\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              47%;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt; .001), as were grade 5 death events (8%\n              <jats:italic toggle=\"yes\">v<\/jats:italic>\n              0%,\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .017).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>Pazopanib compared with placebo significantly improves PFS in patients with progressive epNET, confirming that the VEGF signaling pathway is a valid target for therapy in epNET. However, after integrating the associated risks relative to the benefits, further development of pazopanib in this clinical context is not planned.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/jco-24-02644","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T19:59:26Z","timestamp":1756929566000},"page":"3170-3183","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Randomized Phase II Trial of Pazopanib Versus Placebo in Patients With Advanced Extrapancreatic Neuroendocrine Tumors (Alliance A021202)"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct01841736","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7754-6552","authenticated-orcid":true,"given":"Emily K.","family":"Bergsland","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Geyer","sequence":"additional","affiliation":[{"name":"Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Asmis","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Cancer Centre, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer C.","family":"Behr","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Philip","family":"Kuebler","sequence":"additional","affiliation":[{"name":"Columbus NCI Community Clinical Oncology Research Program, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5923-0677","authenticated-orcid":true,"given":"Priya","family":"Kumthekar","sequence":"additional","affiliation":[{"name":"Northwestern Memorial Hospital, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5305-6193","authenticated-orcid":true,"given":"Gina","family":"Mazza","sequence":"additional","affiliation":[{"name":"Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-5732","authenticated-orcid":true,"given":"Michael L.","family":"Maitland","sequence":"additional","affiliation":[{"name":"Inova Schar Cancer Institute and the University of Virginia Comprehensive Cancer Center, Falls Church, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3566-0450","authenticated-orcid":true,"given":"Donna","family":"Niedzwiecki","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics and Duke Cancer Institute-Biostatistics, Duke University, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3971-2964","authenticated-orcid":true,"given":"Andrew B.","family":"Nixon","sequence":"additional","affiliation":[{"name":"Department of Medicine and Duke Cancer Institute, Duke University, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence Howard","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8405-218X","authenticated-orcid":true,"given":"Jonathan R.","family":"Strosberg","sequence":"additional","affiliation":[{"name":"Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-6548","authenticated-orcid":true,"given":"Alan P.","family":"Venook","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8076-9199","authenticated-orcid":true,"given":"Eileen M.","family":"O'Reilly","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1120-0898","authenticated-orcid":true,"given":"Jeffrey A.","family":"Meyerhardt","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_10_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35463"},{"key":"e_1_3_10_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316158"},{"key":"e_1_3_10_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.8510"},{"key":"e_1_3_10_5_2","doi-asserted-by":"publisher","DOI":"10.4158\/EP151172.OR"},{"key":"e_1_3_10_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.2.600"},{"key":"e_1_3_10_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607427"},{"key":"e_1_3_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00817-X"},{"key":"e_1_3_10_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009290"},{"key":"e_1_3_10_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-021-01030-0"},{"key":"e_1_3_10_11_2","first-page":"Abstract #LBA8","article-title":"A randomized, double-blind, placebo-controlled, multicenter phase III trial of everolimus + octreotide LAR vs palcebo + octreotide LAR in patients with advanced neuroendocrine tumors (RADIANT-2)","volume":"21","author":"Pavel ME","year":"2010","unstructured":"Pavel ME, Hainsworth J, Baudin E, et al: A randomized, double-blind, placebo-controlled, multicenter phase III trial of everolimus + octreotide LAR vs palcebo + octreotide LAR in patients with advanced neuroendocrine tumors (RADIANT-2). 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