Impact of PD-1 inhibitor immunotherapy on survival in patients with newly diagnosed and recurrent glioblastoma: a systematic review of comparative evidence

Introduction : Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. PD-1 inhibitors have shown potential use in GBM. There is some evidence to suggest that programmed death-1 (PD-1) inhibitors may be effective in treating GBM. However, the results of clinical trials conducted to date have been inconclusive, which has led to questions regarding the efficacy of PD-1 inhibitors in this context. Aim : This systematic review aimed to evaluate whether PD-1 inhibitors provide a survival advantage over the standard regimens in GBM. Materials and methods : This review followed the PRISMA guidelines. Comprehensive searches were conducted in PubMed, Scopus, and the Cochrane Library from 2015 to 2025. The extracted data included the study design, sample characteristics, interventions, comparators, and reported survival outcomes. The risk of bias was assessed using the Cochrane RoB 2 tool. Results : Four trials were included in this review. In newly diagnosed GBM, PD-1 inhibitors plus radiotherapy showed an inferior overall survival (OS) rate compared to standard regimens (median OS [mOS] 13.4 vs. 14.9 months, HR 1.31 [95% CI: 1.09-1.58]). PD-1 inhibitors as an adjuvant to temozolomide-based therapy also showed no statistically significant improvement in OS (mOS 11.6 vs. 11.8 months, HR 0.85 [95% CI 0.54-1.33]) or progression-free survival (PFS) (median PFS [mPFS] 7.4 vs. 5.9 months, HR 0.77 [95% CI 0.49- 1.19]) compared to placebo. For recurrent GBM, there was no significant difference in OS between nivolumab and bevacizumab (mOS 11.6 vs. 10.0 months, HR 1.04 [95% CI: 0.83-1.3]). Consistently, PD-1 inhibitors did not demonstrate a survival advantage in either newly diagnosed or recurrent glioblastoma. Conclusion : PD-1 inhibitors showed no statistically significant improvement in OS and PFS in patients with GBM.