{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T16:05:18Z","timestamp":1789488318898,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Combined inhibition of AKT and the androgen receptor (AR) might be more efficacious than AR inhibition alone in biochemical recurrence (BCR) of prostate cancer (PC) by additive effects on the two effector pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>E2809 assigned 108 high\u2010risk BCR patients (1:1, arm\u2010A: arm\u2010B) to two phases with 4\u2010week cycles: first (PreBic) phase (3 cycles), arm\u2010B received AKT inhibitor MK\u20102206 200\u2009mg 2x\/week, arm\u2010A was observation; second phase, bicalutamide (Bic), 50\u2009mg daily, was added to each arm. The PreBic phase assessed whether AKT inhibition changed PSA, reflecting AR activation. Exploratory primary endpoint (EP1) at 6\u20138 Bic cycles and secondary EP2 at cycle 14 compared the proportion of cases with \u2265stable disease (SD) or progressive disease (PD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PreBic phase: 70% arm\u2010B vs 32% arm\u2010A patients had a\u2009\u2265\u200960% PSA rise (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02). MK\u20102206 skin toxicity (38% grade \u2265\u20093) drove high withdrawal prior to EP1. Bic phase: at EP1, inter\u2010arm PSA response (81%\/82%) or PD (19%\/18%) was equal. At EP2, PD was greater in arm\u2010A than arm B (36% vs 11%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). In subgroups defined by PreBic phase PD (PBPD; PSA rise \u2265\u200925%), 9\/16 arm\u2010A vs 0\/7 arm\u2010B cases experienced PD at EP2 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02); overall between PBPD\u2010subgroups, 73% arm\u2010A vs 27% arm\u2010B experienced PD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results suggest that latent improved outcome of high\u2010risk BCR patients (mean PSA doubling time 4.4 months) on combined MK\u20102206+Bic versus Bic alone was attributable to a subgroup identified by crosstalk AR activation secondary to inhibition of AKT. Toxicity may affect tolerance of sustained AKT\u2010AR inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials. gov number, NCT01251861.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70125","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T14:16:28Z","timestamp":1769696188000},"page":"697-709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase II Randomized Study of MK\u20102206 and Bicalutamide in Prostate Cancer Patients With Rising PSA After Primary Therapy (ECOG\u2010ACRIN E2809)"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7382-0111","authenticated-orcid":false,"given":"Anna C.","family":"Ferrari","sequence":"first","affiliation":[{"name":"Montefiore\u2010Einstein Comprehensive Cancer Center Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute \u2013 ECOG\u2010ACRIN Biostatistics Center Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary R.","family":"Hudes","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel S.","family":"Antonarakis","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah M.","family":"Hahn","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary","family":"Ma","sequence":"additional","affiliation":[{"name":"M D Anderson Cancer Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Plimack","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Mayer","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley C.","family":"Carthon","sequence":"additional","affiliation":[{"name":"Emory University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2010Madison Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Carducci","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"DiPaola","sequence":"additional","affiliation":[{"name":"University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000134888.22332.bb"},{"issue":"1","key":"e_1_2_12_3_1","first-page":"14","article-title":"Management of Biochemically Recurrent Prostate Cancer After Local Therapy: Evolving Standards of Care and New Directions","volume":"11","author":"Paller C. 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