Two Cilengitide Regimens in Combination With Standard Treatment for Patients With Newly Diagnosed Glioblastoma and Unmethylated Mgmt Gene Promoter: Results of the Open-Label Controlled Randomized Phase II Core Study
Background: Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. Methods: Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2Ã—/wk; n = 88), intensive cilengitide (2000 mg 5Ã—/wk during wk 1-6, thereafter 2Ã—/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1-6), followed by TMZ maintenance therapy (TMZ/RTâ†’TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. Results: Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P =. 032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P =. 3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. Conclusions: Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RTâ†’TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study.
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Nabors, L. Burt; Fink, Karen L.; Mikkelsen, Tom; Grujicic, Danica; Tarnawski, Rafal; Nam, Do Hyun; Mazurkiewicz, Maria; Salacz, Michael; Ashby, Lynn S.; Zagonel, Vittorina; Depenni, Roberta; Perry, James R.; Hicking, Christine; Picard, Martin; Hegi, Monika E.; Lhermitte, Benoit; and Reardon, David A., "Two Cilengitide Regimens in Combination With Standard Treatment for Patients With Newly Diagnosed Glioblastoma and Unmethylated Mgmt Gene Promoter: Results of the Open-Label Controlled Randomized Phase II Core Study" (2015). Neurology. 14.