{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:34:54Z","timestamp":1790213694034,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 CA190174"],"award-info":[{"award-number":["P01 CA190174"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,3,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>PI3K pathway activation is common in endometrial cancer. We evaluated the safety and efficacy of the dual PI3K\/mTOR inhibitor, LY3023414, in patients with advanced endometrial cancer harboring activating mutations in the PI3K pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a single\u2010arm phase 2 study of monotherapy LY3023414. Eligible patients had advanced endometrial cancer of any grade, prior management with 1\u20104 cytotoxic lines, and PI3K pathway activation prospectively defined as a loss\u2010of\u2010function\n                      <jats:italic>PTEN<\/jats:italic>\n                      alteration or activating alteration in\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      ,\n                      <jats:italic>AKT1<\/jats:italic>\n                      ,\n                      <jats:italic>PIK3R1<\/jats:italic>\n                      ,\n                      <jats:italic>PIK3R2<\/jats:italic>\n                      , or\n                      <jats:italic>MTOR<\/jats:italic>\n                      . The primary objective was best overall response rate (ORR) per RECIST 1.1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010eight patients were treated; histologies included endometroid (39%), carcinosarcoma (25%), serous (21%), and mixed (14%). Patients were heavily pretreated, with a median of 2 prior cytotoxic lines (range, 1\u20103). The most common alterations involved\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      (68%),\n                      <jats:italic>PTEN<\/jats:italic>\n                      (43%), and\n                      <jats:italic>PIK3R1<\/jats:italic>\n                      (32%). In the 25 efficacy\u2010evaluable patients, the ORR was 16% (90% CI, 7%\u2010100%), and the clinical benefit rate was 28% (90% CI, 16%\u2010100%). Four patients had a confirmed partial response, and 2 responses lasted for &gt;9\u00a0months. The median progression\u2010free survival and overall survival were 2.5\u00a0months (95% CI, 1.2\u20103.0) and 9.2\u00a0months (95% CI, 5.0\u201015.9), respectively. The most common all\u2010grade treatment\u2010related adverse events were anemia (71%), hyperglycemia (71%), hypoalbuminemia (68%), and hypophosphatemia (61%). No correlation between molecular alterations and response was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with heavily pretreated advanced endometrial cancer prospectively selected for tumors with activating PI3K pathway mutations, LY3023414 demonstrated modest single\u2010agent activity and a manageable safety profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.32677","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T09:14:45Z","timestamp":1577438085000},"page":"1274-1282","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Phase 2 study of LY3023414 in patients with advanced endometrial cancer harboring activating mutations in the PI3K pathway"],"prefix":"10.1002","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7943-8245","authenticated-orcid":false,"given":"Maria M.","family":"Rubinstein","sequence":"first","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8150-9762","authenticated-orcid":false,"given":"David M.","family":"Hyman","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"},{"name":"Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imogen","family":"Caird","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Won","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krysten","family":"Soldan","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Seier","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia","family":"Iasonos","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William P.","family":"Tew","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"},{"name":"Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roisin E.","family":"O\u2019Cearbhaill","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"},{"name":"Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel N.","family":"Grisham","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"},{"name":"Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martee L.","family":"Hensley","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"},{"name":"Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Troso\u2010Sandoval","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"},{"name":"Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Sabbatini","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"},{"name":"Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Guillen","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Duygu","family":"Selcuklu","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Zimel","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Torrisi","sequence":"additional","affiliation":[{"name":"Department of Radiology Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Aghajanian","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"},{"name":"Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky","family":"Makker","sequence":"additional","affiliation":[{"name":"Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York New York"},{"name":"Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,27]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"SEER Cancer Stat Facts: Uterine Cancer","author":"Surveillance, Epidemiology, and End Results Program","year":"2017"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021423"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.35.15_suppl.3071"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30020-8"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12113"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4333"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0412"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0615"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.381"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.430"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30286"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2014.12.019"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-012-0242-9"},{"issue":"15","key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"5524","DOI":"10.1200\/jco.2013.31.15_suppl.5524","article-title":"Phase II, two\u2010stage, two\u2010arm, PIK3CA mutation stratified trial of MK\u20102206 in recurrent endometrial cancer (EC)","volume":"31","author":"Myers AP","year":"2013","journal-title":"J Clin Oncol"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13948"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813904"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3860"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0343-4"},{"key":"e_1_2_8_21_1","first-page":"1500","article-title":"mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates","volume":"66","author":"O\u2019Reilly KE","year":"2006","journal-title":"Akt"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-15-0996"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-3421"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.240"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2014.12.006"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2006.03.043"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:DRUG.0000026262.77502.31"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.06.013"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.6397"},{"key":"e_1_2_8_31_1","first-page":"337","article-title":"Small molecule inhibitors of DNA\u2010PK for tumor sensitization to anticancer therapy","volume":"68","author":"Pospisilova M","year":"2017","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2620"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1375"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2016.04.019"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2012.03.032"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-011-9794-8"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.32677","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.32677","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.32677","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.32677","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:30:48Z","timestamp":1760265048000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.32677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,27]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,3,15]]}},"alternative-id":["10.1002\/cncr.32677"],"URL":"https:\/\/doi.org\/10.1002\/cncr.32677","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,27]]},"assertion":[{"value":"2019-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}