{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:56:54Z","timestamp":1790535414680,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001111","name":"Cancer Australia","doi-asserted-by":"publisher","award":["1188642"],"award-info":[{"award-number":["1188642"]}],"id":[{"id":"10.13039\/501100001111","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000927","name":"Prostate Cancer Foundation of Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000927","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015539","name":"Australian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004948","name":"Astellas Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1196225"],"award-info":[{"award-number":["1196225"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2016274"],"award-info":[{"award-number":["2016274"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A higher ratio of IGF\u20101:IGF binding protein 1 (IGFBP1) was associated with improved prognosis in the CHAARTED trial of docetaxel in participants with metastatic hormone\u2010sensitive prostate cancer (mHSPC). The ENZAMET trial demonstrated the survival benefit of adding enzalutamide to androgen deprivation therapy (ADT) in mHSPC, and included participants who also received docetaxel as standard of care. The aim of this study was to validate the association between levels of circulating IGF\u20101 and IGFBP1 and survival of ENZAMET participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>IGF\u20101 and IGFBP1 levels were measured in baseline plasma from 845 ENZAMET participants, and associations with clinical progression\u2010free survival (cPFS) and overall survival (OS) were assessed as a post\u2010hoc analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A high baseline plasma ratio of IGF\u20101:IGFBP1 (upper two tertiles) was associated with improved OS (HR 0.75, p 0.008) and improved cPFS (HR 0.82, p 0.034) compared to the lowest tertile. IGF\u20101:IGFBP1 was not predictive of enzalutamide or docetaxel benefit (no significant interaction with treatment arm or docetaxel use). In participants in the enzalutamide arm, IGF\u20101:IGFBP1 was an independent predictor for OS and cPFS in bivariable analysis with docetaxel use. The rate of high volume disease was similar in patients with lower IGF\u20101:IGFBP1 ratio and those with high ratio (~50%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This analysis demonstrated a consistent association of improved prognosis with high IGF\u20101:IGFBP1 in mHSPC, but did not identify which participants benefited from docetaxel when treated with enzalutamide.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70245","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:35:25Z","timestamp":1790534125000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Insulin\u2010Like Growth Factor Axis and Survival in Metastatic Hormone\u2010Sensitive Prostate Cancer: Post\u2010Hoc Analysis From the ENZAMET Phase 3 Trial"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2216-5650","authenticated-orcid":false,"given":"Michael A.","family":"Cilento","sequence":"first","affiliation":[{"name":"South Australian Immunogenomics Cancer Institute Adelaide University Adelaide Australia"},{"name":"Department of Medical Oncology Royal Adelaide Hospital Adelaide Australia"},{"name":"Australia and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4892-6008","authenticated-orcid":false,"given":"Hui\u2010Ming","family":"Lin","sequence":"additional","affiliation":[{"name":"Australia and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Sydney Australia"},{"name":"Garvan Institute of Medical Research Sydney Australia"},{"name":"School of Clinical Medicine University of New South Wales Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Yeung","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.N.","family":"Kim","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Portman","sequence":"additional","affiliation":[{"name":"Australia and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Sydney Australia"},{"name":"Garvan Institute of Medical Research Sydney Australia"},{"name":"School of Clinical Medicine University of New South Wales Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3793-8724","authenticated-orcid":false,"given":"Martin R.","family":"Stockler","sequence":"additional","affiliation":[{"name":"Australia and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Sydney Australia"},{"name":"NHMRC Clinical Trials Centre University of Sydney Camperdown Australia"},{"name":"University of Sydney Camperdown Australia"},{"name":"Department of Medical Oncology Chris O'Brien Lifehouse Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Martin","sequence":"additional","affiliation":[{"name":"The University of Queensland Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Subhash","sequence":"additional","affiliation":[{"name":"Australia and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Yip","sequence":"additional","affiliation":[{"name":"Australia and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Sydney Australia"},{"name":"NHMRC Clinical Trials Centre University of Sydney Camperdown Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2698-3220","authenticated-orcid":false,"given":"Lisa M.","family":"Butler","sequence":"additional","affiliation":[{"name":"South Australian Immunogenomics Cancer Institute Adelaide University Adelaide Australia"},{"name":"Australia and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C.","family":"Marschner","sequence":"additional","affiliation":[{"name":"NHMRC Clinical Trials Centre University of Sydney Camperdown Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Meikle","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute Melbourne Australia"},{"name":"Department of Cardiovascular Research 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