BEZ235用于依维莫司耐药的晚期胰腺神经内分泌肿瘤患者的II期研究。
A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours.
作者信息
Fazio Nicola, Buzzoni Roberto, Baudin Eric, Antonuzzo Lorenzo, Hubner Richard A, Lahner Harald, DE Herder Wouter W, Raderer Markus, Teulé Alexandre, Capdevila Jaume, Libutti Steven K, Kulke Matthew H, Shah Manisha, Dey Debarshi, Turri Sabine, Aimone Paola, Massacesi Cristian, Verslype Chris
机构信息
European Institute of Oncology, Milan, Italy
IRCCS National Tumor Institute, Milan, Italy.
出版信息
Anticancer Res. 2016 Feb;36(2):713-9.
BACKGROUND
This was a two-stage, phase II trial of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor BEZ235 in patients with everolimus-resistant pancreatic neuroendocrine tumours (pNETs) (NCT01658436).
PATIENTS AND METHODS
In stage 1, 11 patients received 400 mg BEZ235 orally twice daily (bid). Due to tolerability concerns, a further 20 patients received BEZ235 300 mg bid. Stage 2 would be triggered by a 16-week progression-free survival (PFS) rate of ≥60% in stage 1.
RESULTS
As of 30 June, 2014, 29/31 patients had discontinued treatment. Treatment-related grade 3/4 adverse events were reported in eight (72.7%) patients at 400 mg and eight (40.0%) patients at 300 mg, including hyperglycaemia, diarrhoea, nausea, and vomiting. The estimated 16-week PFS rate was 51.6% (90% confidence interval=35.7-67.3%).
CONCLUSION
BEZ235 was poorly tolerated by patients with everolimus-resistant pNETs at 400 and 300 mg bid doses. Although evidence of disease stability was observed, the study did not proceed to stage 2.
背景
这是一项双阶段的II期试验，研究双重磷脂酰肌醇3激酶/雷帕霉素哺乳动物靶点抑制剂BEZ235用于依维莫司耐药的胰腺神经内分泌肿瘤（pNETs）患者（NCT01658436）。
患者与方法
在第1阶段，11例患者接受BEZ235口服，400 mg，每日两次（bid）。由于耐受性问题，另外20例患者接受BEZ235 300 mg bid。如果第1阶段无进展生存期（PFS）率≥60%达16周，则触发第2阶段。
结果
截至2014年6月30日，31例患者中有29例停止治疗。400 mg组有8例（72.7%）患者、300 mg组有8例（40.0%）患者报告了与治疗相关的3/4级不良事件，包括高血糖、腹泻、恶心和呕吐。估计16周PFS率为51.6%（90%置信区间=35.7 - 67.3%）。
结论
对于依维莫司耐药的pNETs患者，BEZ235剂量为400 mg和300 mg bid时耐受性较差。尽管观察到疾病稳定的证据，但该研究未进入第2阶段。
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