The standard treatment for patients with newly diagnosed glioblastoma is based on surgical resection associated with radiotherapy (RT) and temozolomide (TMZ). However, the effectiveness of this approach is limited by the intratumoral heterogeneity and by the enzyme MGMT (O6-methylguanine-DNA methyltransferase) activity itself. Immune checkpoint inhibitors (ICIs) emerge as a compelling therapeutic strategy combined with RT and TMZ for these patients.

A systematic review and meta-analysis of English-language studies from PubMed, Embase, and LILACS were conducted to assess the efficacy and safety of ICIs in combination with the standard treatment for newly diagnosed glioblastoma. The primary outcomes were overall survival (OS), progression-free survival (PFS) and treatment-related adverse events. Secondary endpoints were OS and PFS according to extent of surgical resection (ESR), and adverse events for grade 3 or above. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled. Quality assessment and risk of bias were performed according to Cochrane recommendations.

Three randomized controlled trials (RCTs) with 938 patients were included, 506 (54%) of whom had been administered ICI + TMZ + RT. OS (HR: 1.06; 95% CI:0.92–1.21; p = 0.41; I² = 0%) and PFS (HR: 1.06; 95% CI: 0.88–1.27; p = 0.55; I² = 48%) were not significantly different between the ICIs and the standard treatment alone groups. Headache, as an adverse event, occurred significantly more frequently in the ICI group (OR: 1.58; 95% CI: 1.04–2.41; p = 0.03; I² = 0%). Other adverse events showed no significant differences between the groups. No subgroup analysis – neither OS nor PFS stratified by ESR – demonstrated significant differences between treatment groups.

This meta-analysis demonstrates the addition of ICIs to TMZ plus RT does not confer statistically significant survival benefits in patients with newly diagnosed glioblastoma and are significantly associated with an increased incidence of headache when compared to the standard treatment alone. This signal was not accompanied by a significant rise in other adverse events, suggesting the overall safety remains manageable.