依维莫司
奥曲肽
脑膜瘤
医学
相(物质)
内科学
肿瘤科
放射科
物理
生长抑素
量子力学
作者
Thomas Graillon,Marc Sanson,Chantal Campello,Ahmed Idbaïh,Matthieu Peyre,Hadrien Peyrière,Noémie Basset,Didier Autran,Catherine Roche‐Lestienne,M. Kalamaridès,Pierre‐Hugues Roche,S. Fuentès,Émeline Tabouret,Maryline Barrié,Anita Cohen,Mohamed Boucékine,Mohamed Boucékine,Karine Baumstarck,Dominique Figarella‐Branger,Anne Barlier,H. Dufour,Olivier Chinot
标识
DOI:10.1158/1078-0432.ccr-19-2109
摘要
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 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.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).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.
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