A network meta-analysis of treatment for newly diagnosed glioblastoma based on radiotherapy plus temozolomide

ABSTRACT

Background & Objective: Radiotherapy and temozolomide are the standard therapy for newly diagnosed glioblastoma multiforme (GBM). However, it is unclear whether adding another agent to the commonly used radiotherapy-temozolomide (RT + TMZ) benefits newly diagnosed GBM patients. The present network meta-analysis aimed to assess the efficacy of combining other agents with RT + TMZ for GBM treatment. Methods: A comprehensive literature search was conducted on PubMed, EMBASE.com, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to September 23, 2014, to include all randomized controlled trials of RT + TMZ-based therapy in GBM patients. Pairwise and network meta-analyses were performed to compare the therapeutic regimens. Results: Seventeen studies involving 4,148 patients were identified. The results of pairwise meta-analysis indicated no significant differences among most comparison groups, except for bevacizumab + RT + TMZ versus RT + TMZ for progression-free survival (hazard ratio [HR] = 0.71, 95% confidence interval [CI] 0.59–0.86; P = 0.000) and RT + TMZ versus RT alone for overall survival (HR = 0.71, 95% CI 0.58–0.88; P = 0.001). The results of network meta-analysis also showed no significant differences in most comparisons; however, adverse events were more common among patients receiving additional therapeutic agents other than RT + TMZ. The ranking probability analysis indicated that bevacizumab + RT + TMZ and nimustine + cisplatin + RT + TMZ were associated with the best progression-free and overall survival, but they also caused the most adverse events in GBM patients. RT + bevacizumab + irinotecan had the highest probability of being the best regimen for minimizing adverse events. Conclusions: The addition of other targeted agents, particularly bevacizumab and nimustine, to RT + TMZ could be slightly effective for the treatment of newly diagnosed GBM patients; however, adverse events remained common.