{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:41:17Z","timestamp":1792802477121,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000801","name":"Bayer HealthCare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000801","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,4,15]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Biliary tract cancer (BTC) has a poor prognosis despite treatment with first\u2010line gemcitabine and cisplatin. In BTC, PI3K\/AKT pathway activation has been shown to increase resistance to chemotherapy, which may be overcome with PI3K inhibition. This phase 2 study evaluated the safety and efficacy of copanlisib, a PI3K inhibitor, with gemcitabine and cisplatin in advanced BTCs. The role of PTEN expression in outcomes was also explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with advanced\/unresectable BTC received gemcitabine, cisplatin, and copanlisib as their first\u2010line treatment. The primary endpoint was progression\u2010free survival (PFS) at 6 months. Secondary endpoints were the response rate (RR), median overall survival (OS)\/PFS, and safety profile. An assessment of PTEN expression by immunohistochemistry was also performed along with molecular profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010four patients received at least 1 dose of the study drug. The PFS rate at 6 months was 51%; the median OS was 13.7 months (95% CI, 6.8\u201018.0 months), and the median PFS was 6.2 months (95% CI, 2.9\u201010.1 months). Nineteen patients were evaluable for RR: 6 patients achieved a partial response (31.6%), and 11 (57.9%) had stable disease. The most common grade 3\/4 adverse events were a decreased neutrophil count (45.83%), anemia (25%), increased lipase (25%), and hypertension (20.8%). Twenty patients had tissue evaluable for the PTEN status. The PFS for low (n = 9) and high PTEN expression (n = 11) was 8.5 and 4.6 months, respectively (<jats:italic>P<\/jats:italic> = .19). The median OS for low and high PTEN expression groups was 17.9 and 7.0 months, respectively (<jats:italic>P<\/jats:italic> = .19).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The addition of copanlisib to gemcitabine and cisplatin does not improve PFS at 6 months. However, future studies using PTEN as a potential biomarker should be considered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Lay Summary<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n\n<jats:list-item><jats:p>The addition of copanlisib, a PI3K inhibitor, to standard chemotherapy for advanced biliary tract cancers was assessed for efficacy and safety. Twenty\u2010four patients with advanced biliary tract cancer received treatment in this study.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>There was no difference in survival with the addition of copanlisib in comparison with standard chemotherapy.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Copanlisib may be more effective and increase survival in patients with low PTEN expression levels. Further studies are needed to confirm this. No unexpected adverse events occurred.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33364","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T22:09:05Z","timestamp":1607465345000},"page":"1293-1300","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Phase 2 study of copanlisib in combination with gemcitabine and cisplatin in advanced biliary tract cancers"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1656-368X","authenticated-orcid":false,"given":"Elaine S.","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Oncology H. Lee Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biwei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics H. Lee Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongphil","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics H. Lee Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-2414","authenticated-orcid":false,"given":"Taymeyah E.","family":"Al\u2010Toubah","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology H. Lee Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4277-0153","authenticated-orcid":false,"given":"Rutika","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology H. Lee Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Centeno","sequence":"additional","affiliation":[{"name":"Department of Pathology H. Lee Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8448-844X","authenticated-orcid":false,"given":"Richard D.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology H. Lee Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000453013"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.10.013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4137\/CMO.S32821"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908721"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-013-0945-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-9-3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx289"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.4648"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813904"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-0993-T"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.428"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605211"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-1084"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0017"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.01.009"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2015.09.007"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.133"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2013.04.013"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.08.2034"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000367961"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3465"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gore.2019.100532"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-0954-x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-18-0374"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw282"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.10.018"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33364","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.33364","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33364","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:11:03Z","timestamp":1760263863000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.33364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,8]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,4,15]]}},"alternative-id":["10.1002\/cncr.33364"],"URL":"https:\/\/doi.org\/10.1002\/cncr.33364","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,8]]},"assertion":[{"value":"2020-09-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}