{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:00:16Z","timestamp":1785265216502,"version":"3.55.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To investigate the efficacy and safety of buparlisib, an oral pan-PI3K inhibitor, in relapsed or refractory thymomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a single center, single arm, open label phase II trial of buparlisib in patients with recurrent thymoma who have progressed after at least one prior line of treatment. The primary endpoint was objective response rate (complete response [CR] + partial response [PR]). Secondary endpoints included toxicity; progression free survival (PFS); overall survival (OS); disease control rate (DCR), i.e., the percentage of patients who achieve either PR or CR or stable disease [SD] for at least 4 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between 10\/13\/2014 and 1\/18\/2017, 14 patients with stage IV disease were enrolled. Median age was 58y (23\u201374). 71% were females and 71% white. All patients had WHO B2 (29%) or B3 (71%) thymoma. Patients received buparlisib for a median of 4.5m (2\u201333). At a median follow up of 16.6m (2.4\u201331.3), onr patients (7%) achieved a PR. DCR was 50%. Median PFS was 11.1m (95% CI 2.9 \u2013 18.8). Median OS, updated as of March, 2021 was 22.5m (10.7\u201331.3). Most common grade 3-4 adverse events related to buparlisib were dyspnea (21%), rash (14%), elevated transaminases (14%), cough (7%), pneumonitis (7%), anxiety (7%), fatigue (7%) and hyperglycemia (7%). Reasons for treatment discontinuation included progression of disease (n= 5), rash (n=4), pulmonary toxicity (n=3), sinusitis (n=1), and disseminated toxoplasmosis plus autoimmune cholangitis (n=1). As of 3\/2021, 8 patients have died, 7 due to disease progression and 1 due to central nervous system toxoplasmosis and autoimmune cholangitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Buparlisib showed modest activity in patients with relapsed or refractory thymomas. Further investigation of PI3K pathway targeted therapy in thymoma is warranted. (clinicaltrials.gov ID: NCT02220855).<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:uri>clinicaltrials.gov<\/jats:uri>, identifier (NCT02220855)<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2022.891383","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T08:35:01Z","timestamp":1666082101000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["A phase II study of buparlisib in relapsed or refractory thymomas"],"prefix":"10.3389","volume":"12","author":[{"given":"Mohammad I.","family":"Abu Zaid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Radovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Althouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron J.","family":"Spittler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Solzak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Badve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Sr","given":"Patrick J.","family":"Loehrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2008.12.095","article-title":"Thymomas: Review of current clinical practice","volume":"87","author":"Tomaszek","year":"2009","journal-title":"Ann Thorac Surg"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.3.814","article-title":"Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phase II study of the European organization for research and treatment of cancer lung cancer cooperative group","volume":"14","author":"Giaccone","year":"1996","journal-title":"J Clin Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010601)91:11<2010::AID-CNCR1226>3.0.CO;2-2","article-title":"Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: An intergroup trial","volume":"91","author":"Loehrer","year":"2001","journal-title":"Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.9607","article-title":"Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma","volume":"29","author":"Lemma","year":"2011","journal-title":"J Clin Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.lungcan.2018.10.018","article-title":"Systemic treatments for thymoma and thymic carcinoma: A systemic review","volume":"126","author":"Berghmans","year":"2018","journal-title":"Lung Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3181f21114","article-title":"Targeted therapy for advanced thymic tumors","volume":"5","author":"Rajan","year":"2010","journal-title":"J Thorac Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.425","article-title":"A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type a and AB thymomas","volume":"114","author":"Radovich","year":"2016","journal-title":"Br J Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.04.013","article-title":"PI3K as a potential therapeutic target in thymic epithelial tumors","volume":"11","author":"Alberobello","year":"2016","journal-title":"J Thorac Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197655","article-title":"Activation of the mTOR\/ akt pathway in thymic epithelial cells derived from thymomas","volume":"14","author":"Maury","year":"2019","journal-title":"PLoS One"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.4078","article-title":"Phase II study of everolimus in patients with thymoma and thymic carcinoma previously treated with cisplatin-based chemotherapy","volume":"36","author":"Zucali","year":"2018","journal-title":"J Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1186\/s13059-018-1578-y","article-title":"CODEX2: Full-spectrum copy number variation detection by high-throughput DNA sequencing","volume":"19","author":"Jiang","year":"2018","journal-title":"Genome Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.07.094","article-title":"A phase II study of pemetrexed in patients with recurrent thymoma and thymic carcinoma","volume":"13","author":"Gbolahan","year":"2018","journal-title":"J Thorac Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/path.3995","article-title":"In hepatocellular carcinoma miR-519d is up-regulated by p53 and DNA hypomethylation and targets CDKN1A\/p21, PTEN, AKT3 and TIMP2","volume":"227","author":"Fornari","year":"2012","journal-title":"J Pathol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25367","article-title":"Insulin-like growth factor-1 receptor and phosphorylated AKT-serine 473 expression in 132 resected thymomas and thymic carcinomas","volume":"116","author":"Zucali","year":"2010","journal-title":"Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0838-6","article-title":"Copanlisib: First global approval","volume":"77","author":"Markham","year":"2017","journal-title":"Drugs"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-1013-4","article-title":"Duvelisib: First global approval","volume":"78","author":"Blair","year":"2018","journal-title":"Drugs"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01161-6","article-title":"Apelisib: First global approval","volume":"79","author":"Markham","year":"2019","journal-title":"Drugs"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.891383\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T08:35:03Z","timestamp":1666082103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.891383\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,18]]},"references-count":17,"alternative-id":["10.3389\/fonc.2022.891383"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.891383","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,18]]},"article-number":"891383"}}