A phase II study of buparlisib in relapsed or refractory thymomas

• Type of Material: Article
• Authors: Mohammad I Abu Zaid, Indiana University; Milan Radovich, Caris Life Science, Dallas, TX, United States; Sandra Althouse, Indiana University; Hao Liu, Indiana University; Aaron J Spittler, Indiana University; Jeffrey Solzak, Caris Life Science, Dallas, TX, United States; Sunil Badve, Emory University; Patrick J Loehrer Sr, Indiana University
• Language: English
• Date: 2022-10-18
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Abu Zaid, Radovich, Althouse, Liu, Spittler, Solzak, Badve and Loehrer
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fonc.2022.891383
• Title of Journal or Parent Work: FRONTIERS IN ONCOLOGY
• Volume: 12
• Start Page: 891383
• End Page: 891383
• Grant/Funding Information: This work was supported by the National Cancer Institute Award CA082709. The authors also declare that this study received funding from Novartis in the form of the investigational drug. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
• Keywords: buparlisib; PI3Kinase inhibitor; ETOPOSIDE; THYMIC CARCINOMA; thymic epithelial tumors; Life Sciences & Biomedicine; Akt (PI3K; Oncology; phosphoinositide-3-kinase; thymoma; Science & Technology; Akt) pathway; CISPLATIN
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Biostatistics

Abstract

Purpose: To investigate the efficacy and safety of buparlisib, an oral pan-PI3K inhibitor, in relapsed or refractory thymomas. Methods: 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. Results: Between 10/13/2014 and 1/18/2017, 14 patients with stage IV disease were enrolled. Median age was 58y (23–74). 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 (2–33). At a median follow up of 16.6m (2.4–31.3), onr patients (7%) achieved a PR. DCR was 50%. Median PFS was 11.1m (95% CI 2.9 – 18.8). Median OS, updated as of March, 2021 was 22.5m (10.7–31.3). 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. Conclusion: 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). Clinical trial registration: clinicaltrials.gov, identifier (NCT02220855).