You have to answer a biomedical question in binary format, i.e. only yes and no are the only acceptable answer formats. A list of paragraphs is provided as context to help you answer the question.

Question: Does Enzastaurin improve survival of glioblastoma patients?

Context: RESULTS: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056).
Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy.
So far, inhibition of angiogenesis by compounds such as bevacizumab, cediranib, enzastaurin or cilengitide as well as alternative dosing schedules of temozolomide did not prolong survival, neither at primary diagnosis nor at recurrent disease.
Despite promising phase II clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in four randomized phase III trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma.
EXPERT OPINION: Enzastaurin and cediranib failed in randomized Phase III trials in recurrent glioblastoma, aflibercept in Phase II.
Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.
Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P < or = .001).<br><b>CONCLUSION</b>: Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.<br>
Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.
Enzastaurin has anti-glioma activity in patients with recurrent high-grade glioma, but does not appear to have enough single-agent activity to be useful as monotherapy.
Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy.
CONCLUSION Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.
glioblastomas are highly vascularized tumors and various antiangiogenic drugs have been investigated in clinical trials showing unclear results we performed a systematic review and a meta analysis to clarify and evaluate their effectiveness in glioblastoma patients we searched relevant published and unpublished randomized clinical trials analyzing antiangiogenic drugs versus chemotherapy in glioblastoma patients from january 2006 to january 2016 in medline web of science asco esmo and sno databases fourteen randomized clinical trials were identified 7 with bevacizumab 2 cilengitide 1 enzastaurin 1 dasatinib 1 vandetanib 1 temsirolimus 1 cediranib including 4330 patients antiangiogenic drugs showed no improvement in overall survival with a pooled hr of 1 00 a trend for an inferior outcome in terms of overall survival was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone hr 1 24 p 0 056 bevacizumab did not improve overall survival twelve trials 4113 patients were analyzed for progression free survival among antiangiogenic drugs only bevacizumab demonstrated an improvement of progression free survival hr 0 63 p 0 001 both alone hr 0 60 p 0 003 or in combination to chemotherapy hr 0 63 p 0 001 both as first line treatment hr 0 70 p 0 001 or in recurrent disease hr 0 52 p 0 001 antiangiogenic drugs did not improve overall survival in glioblastoma patients either as first or second line treatment and either as single agent or in combination with chemotherapy among antiangiogenic drugs only bevacizumab improved progression free survival regardless of treatment line both as single agent or in combination with chemotherapy.
glioblastoma is characterized by high expression levels of proangiogenic cytokines and microvascular proliferation highlighting the potential value of treatments targeting angiogenesis antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action ultimately however alternative proangiogenic signal transduction pathways are activated leading to the development of resistance even in tumors that initially respond the identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority despite promising phase ii clinical trial results and patient benefit in terms of clinical improvement and longer progression free survival an overall survival benefit has not been demonstrated in four randomized phase iii trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma however future studies are warranted predictive markers may allow appropriate patient enrichment combination with chemotherapy may ultimately prove successful in improving overall survival and novel agents targeting multiple proangiogenic pathways may prove effective.
this phase iii open label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma who grade 4 patients were randomly assigned 2 1 to receive 6 week cycles of enzastaurin 500 mg d 1 125 mg loading dose day 1 or lomustine 100 to 130 mg m 2 day 1 assuming a 45 improvement in progression free survival pfs 397 patients were required to provide 80 power to achieve statistical significance at a one sided level of 025 enrollment was terminated at 266 patients enzastaurin n 174 lomustine n 92 after a planned interim analysis for futility patient characteristics were balanced between arms median pfs 1 5 v 1 6 months hazard ratio hr 1 28 95 ci 0 97 to 1 70 overall survival 6 6 v 7 1 months hr 1 20 95 ci 0 88 to 1 65 and 6 month pfs rate p 13 did not differ significantly between enzastaurin and lomustine respectively stable disease occurred in 38 5 and 35 9 of patients and objective response occurred in 2 9 and 4 3 of patients respectively time to deterioration of physical and functional well being and symptoms did not differ between arms hr 1 12 p 54 four patients discontinued enzastaurin because of drug related serious adverse events aes eleven patients treated with enzastaurin died on study four because of aes one was drug related all four deaths that occurred in patients receiving lomustine were disease related grade 3 to 4 hematologic toxicities were significantly higher with lomustine 46 events than with enzastaurin one event p or 001 enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.
this study s primary objective was evaluation of the progression free survival rate at 6 months pfs 6 in patients with newly diagnosed glioblastoma without o 6 methylguanine dna methyltransferase mgmt promoter hypermethylation postsurgically treated with enzastaurin before and concomitantly with radiation therapy followed by enzastaurin maintenance therapy pfs 6 of at least 55 was set to be relevant compared with the data of the eortc 26981 22981 ncic ce 3 trial adult patients with a life expectancy of at least 12 weeks who were newly diagnosed with a histologically proven supratentorial glioblastoma without mgmt promoter hypermethylation were eligible patients were treated with enzastaurin prior to concomitantly with and after standard partial brain radiotherapy here we report on a multicenter open label uncontrolled phase ii study of patients with newly diagnosed glioblastoma without mgmt promoter hypermethylation treated with enzastaurin and radiation therapy within 4 study periods pfs 6 was 53 6 95 confidence interval ci 39 8 65 6 the median overall survival was 15 0 months 95 ci 11 9 17 9 for all patients 3 9 months 95 ci 0 8 9 0 for patients with biopsy 15 4 months 95 ci 10 1 17 9 for patients with partial resection and 18 9 months 95 ci 13 9 28 5 for patients with complete resection the safety profile in this study was as expected from previous trials and the therapy was well tolerated pfs 6 missed the primary planned outcome of 55 the secondary exploratory analysis according to resection status of the different subgroups of patients with biopsies partial resection and complete resection demonstrates the strong prognostic influence of resection on overall survival.
we evaluated the efficacy of combination enzastaurin ly317615 and bevacizumab for recurrent malignant gliomas and explored serologic correlates we enrolled 81 patients with glioblastomas gbm n 40 and anaplastic gliomas ag n 41 patients received enzastaurin as a loading dose of 1125 mg followed by 500 or 875 mg daily for patients on non enzyme inducing or enzyme inducing antiepileptics respectively patients received bevacizumab 10 mg kg intravenously biweekly clinical evaluations were repeated every 4 weeks magnetic resonance imaging was obtained at baseline and every 8 weeks from treatment onset phosphorylated glycogen synthase kinase gsk 3 levels from peripheral blood mononuclear cells pbmcs were checked with each mri median overall survival was 7 5 and 12 4 months for glioblastomas and anaplastic glioma cohorts with median progression free survivals of 2 0 and 4 4 months respectively of gbm patients 3 40 7 5 were not evaluable while 8 37 22 had partial or complete response and 20 37 54 had stable disease for 2 months of the 39 evaluable ag patients 18 46 had an objective response and 16 41 had stable disease for 2 months the most common grade 3 toxicities were lymphopenia 15 hypophosphatemia 8 8 and thrombotic events 7 5 two 2 5 gbm patients died suddenly another death 1 3 occurred from intractable seizures phosphorylated gsk 3 levels from pbmcs did not correlate with treatment response a minimally important improvement in health related quality of life was self reported in 7 9 24 29 2 37 5 early response based on levin criteria was significantly associated with significantly longer progression free survival for glioblastomas enzastaurin ly317615 in combination with bevacizumab for recurrent malignant gliomas is well tolerated with response and progression free survival similar to bevacizumab monotherapy.
no