Optimal treatment strategy for adult patients with newly diagnosed glioblastoma: a systematic review and network meta-analysis.

To compare the efficacy and safety of treatments based on the Stupp protocol for adult patients with newly diagnosed glioblastoma and to determine the optimal treatment option for patients with different O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation statuses. We estimated hazard ratios (HRs) for overall survival (OS) and odds ratios (ORs) for adverse events of grade 3 or higher (AEs ≥ 3). Twenty-one randomized controlled trials involving 6478 patients treated with 21 different treatment strategies were included. Results of the pooled HRs indicated tumor-treating fields (TTF) combined with the Stupp protocol resulted in the most favorable OS for patients with and without MGMT promoter methylation. Subgroup analyses by the two MGMT promoter statuses indicated that lomustine­temozolomide plus radiotherapy or TTF combination therapy was associated with the best OS for patients with methylated MGMT promoter (HR, 1.03; 95% credible interval [CI], 0.54–1.97), and standard cilengitide combination therapy or TTF combination treatment was associated with the best OS for patients with unmethylated MGMT promoter (HR, 1.05; 95% CI, 0.67–1.64). Regarding AEs ≥ 3, there were no significant differences in pooled ORs. However, Bayesian ranking profiles that demonstrated intensive cilengitide combination therapy and TTF combination therapy have a similar possibility to cause the least toxicity. These results indicated that TTF combination therapy was associated with increased survival, irrespective of the MGMT promoter methylation status, and a relatively tolerated safety profile compared with other combination treatments. The optimal treatment option for glioblastoma patients with different MGMT promoter methylation statuses was different.