Abu Zaid Mohammad I, Radovich Milan, Althouse Sandra, Liu Hao, Spittler Aaron J, Solzak Jeffrey, Badve Sunil, Loehrer Patrick J
Department of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United States.
Caris Life Science, Dallas, TX, United States.
Front Oncol. 2022 Oct 18;12:891383. doi: 10.3389/fonc.2022.891383. eCollection 2022.
To investigate the efficacy and safety of buparlisib, an oral pan-PI3K inhibitor, in relapsed or refractory thymomas.
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.
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.
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).
clinicaltrials.gov, identifier (NCT02220855).
研究口服泛PI3K抑制剂布帕利昔布用于复发或难治性胸腺瘤的疗效和安全性。
这是一项单中心、单臂、开放标签的II期试验，研究对象为复发胸腺瘤患者，这些患者在至少接受过一线治疗后病情进展。主要终点是客观缓解率（完全缓解[CR]+部分缓解[PR]）。次要终点包括毒性；无进展生存期（PFS）；总生存期（OS）；疾病控制率（DCR），即达到PR或CR或疾病稳定[SD]至少4个月的患者百分比。
在2014年10月13日至2017年1月18日期间，纳入了14例IV期疾病患者。中位年龄为58岁（23 - 74岁）。71%为女性，71%为白人。所有患者均为世界卫生组织（WHO）B2型（29%）或B3型（71%）胸腺瘤。患者接受布帕利昔布治疗的中位时间为4.5个月（2 - 33个月）。中位随访16.6个月（2.4 - 31.3个月）时，1例患者（7%）达到PR。DCR为50%。中位PFS为11.1个月（95%置信区间2.9 - 18.8）。截至2021年3月更新的中位OS为22.5个月（10.7 - 31.3）。与布帕利昔布相关的最常见3 - 4级不良事件为呼吸困难（21%）、皮疹（14%）、转氨酶升高（14%）、咳嗽（7%）、肺炎（7%）、焦虑（7%）、疲劳（7%）和高血糖（7%）。治疗中断的原因包括疾病进展（n = 5）、皮疹（n = 4）、肺部毒性（n = 3）、鼻窦炎（n = 1）以及播散性弓形虫病加自身免疫性胆管炎（n = 1）。截至2021年3月，8例患者死亡，7例死于疾病进展，1例死于中枢神经系统弓形虫病和自身免疫性胆管炎。
布帕利昔布在复发或难治性胸腺瘤患者中显示出适度活性。有必要对PI3K通路靶向治疗胸腺瘤进行进一步研究。（临床试验.gov标识符：NCT02220855）。
clinicaltrials.gov，标识符（NCT02220855）。
