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.

比较基于 Stupp 方案的新诊断胶质母细胞瘤成人患者的疗效和安全性，并确定具有不同 O-6-甲基鸟嘌呤-DNA 甲基转移酶 ( MGMT ) 启动子甲基化状态的患者的最佳治疗方案。我们估计了总生存期 (OS) 的风险比 (HR) 和 3 级或更高级别不良事件 (AE ≥ 3) 的优势比 (OR)。纳入了 21 项随机对照试验，涉及 6478 名接受 21 种不同治疗策略治疗的患者。汇总 HR 的结果表明，肿瘤治疗野 (TTF) 与 Stupp 方案相结合，为有和没有MGMT启动子甲基化的患者带来了最有利的 OS 。两个MGMT 的亚组分析启动子状态表明洛莫司汀替莫唑胺加放疗或 TTF 联合治疗与甲基化MGMT启动子（HR，1.03；95% 可信区间 [CI]，0.54-1.97）和标准西仑吉肽联合治疗或 TTF 联合治疗患者的最佳 OS 相关与未甲基化MGMT启动子的患者的最佳 OS 相关（HR，1.05；95% CI，0.67-1.64）。对于 AE ≥ 3，合并 OR 没有显着差异。然而，证明强化西仑吉肽联合治疗和 TTF 联合治疗的贝叶斯排名曲线具有相似的可能性，导致毒性最小。这些结果表明，无论MGMT，TTF 联合治疗与生存率增加有关启动子甲基化状态，以及与其他联合治疗相比相对耐受的安全性。具有不同MGMT启动子甲基化状态的胶质母细胞瘤患者的最佳治疗方案是不同的。