Everolimus and Octreotide for Patients with Recurrent Meningioma: Results from the Phase II CEVOREM Trial
Everolimus and Octreotide for Patients with Recurrent Meningioma: Results from the Phase II CEVOREM Trial
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DOI：
10.1158/1078-0432.ccr-19-2109
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发表时间：
2020-02-01
影响因子：
11.5
通讯作者：
Chinot, Olivier Louis
中科院分区：
文献类型：
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作者：
Graillon, Thomas;Sanson, Marc;Chinot, Olivier Louis
目的：手术/放疗后进展的侵袭性脑膜瘤代表了未满足的医疗需求。SSTR 2A受体的强和恒定表达以及Pi 3 K/Akt/mTOR通路的激活已在脑膜瘤中得到证实。依维莫司（一种mTOR抑制剂）和奥曲肽（一种生长抑素激动剂）的组合在体外显示出相加的抗肿瘤作用。II期CEVOREM试验研究了这种组合对复发性meningoma.Patients和方法的疗效：记录复发性肿瘤进展不适合进一步手术/放疗的患者有资格接受奥曲肽（30 mg/d，第1天）和依维莫司（10 mg/d，第1-28天）。主要终点为6个月无进展生存率（PFS 6）。次要终点为总生存期、缓解率、肿瘤生长率（根据中心审查）和safety.Results：共入组20例患者，其中2例为WHO I级肿瘤，10例为WHO II级肿瘤，8例为WHO III级肿瘤;此外，4例患者携带NF 2种系突变。总体PFS 6为55% [95%置信区间（CI），31.3%-73.5%]，6个月和12个月总体生存率分别为90%（95% CI，65.6%-97.4%）和75%（95% CI，50.0%-88.7%）。在78%的肿瘤中，在3个月时观察到生长速率的显著降低（>50%）。中位肿瘤生长率从入组前的16.6%/3个月下降到治疗后3个月的0.02%/3个月（P < 0.0002）和6个月的0.48%/3个月（P < 0.0003）。结论：依维莫司和奥曲肽联合治疗侵袭性脑膜瘤与临床和放射学活性相关，值得进一步研究。肿瘤体积增长率的降低应被视为一个补充和敏感的终点，以选择潜在的有效药物治疗复发性脑膜瘤。
Purpose: Aggressive meningiomas that progress after surgery/ radiotherapy represent an unmet medical need. Strong and constant expression of SSTR2A receptors and activation of the Pi3K/Akt/mTOR pathway have been demonstrated in meningiomas. The combination of everolimus, an mTOR inhibitor, and octreotide, a somatostatin agonist, has shown additive antitumor effect in vitro. The phase II CEVOREM trial investigated the efficacy of this combination on recurrent meningiomas.Patients and Methods: Patients with documented recurrent tumor progression ineligible for further surgery/radiotherapy were eligible to receive octreotide (30 mg/d, day 1) and everolimus (10 mg/d, days 1-28). The primary endpoint was the 6-month progression-free survival rate (PFS6). The secondary endpoints were overall survival, response rate, tumor growth rate according to central review, and safety.Results: A total of 20 patients were enrolled, including 2 with World Health Organization (WHO) grade I tumors, 10 with WHO grade II tumors, and 8 with WHO grade III tumors; furthermore, 4 patients harbored NF2 germline mutation. The overall PFS6 was 55% [95% confidence interval (CI), 31.3%-73.5%], and overall 6- and 12-month survival rates were 90% (95% CI, 65.6%-97.4%) and 75% (95% CI, 50.0%-88.7%), respectively. A major decrease (>50%) was observed in the growth rate at 3 months in 78% of tumors. The median tumor growth rate decreased from 16.6%/3 months before inclusion to 0.02%/3 months at 3 months (P < 0.0002) and 0.48%/3 months at 6 months after treatment (P < 0.0003).Conclusions: The combination of everolimus and octreotide was associated with clinical and radiological activity in aggressive meningiomas and warrants further studies. Decrease in the tumor volume growth rate should be considered a complementary and sensitive endpoint to select potentially effective drugs for recurrent meningiomas.