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Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Immunotherapy failure in glioblastoma: A systematic review and meta-analysis of randomized controlled trials
1Department of Paediatric Neurosurgery, Children's Hospital named after prof. dr med. Jan Bogdanowicz in Warsaw, Poland; Faculty of Medicine, Lazarski Medical University in Warsaw, Poland.
Background:
Immunotherapy has transformed outcomes in several solid tumors but has repeatedly failed to demonstrate benefit in glioblastoma. Early-phase signals of activity have not translated into improved survival in randomized trials, creating uncertainty regarding its true clinical value.
Methods:
A systematic review and random-effects meta-analysis of randomized controlled trials (RCTs) evaluating immunotherapy in adult glioblastoma was conducted in accordance with PRISMA 2020. PubMed, Embase, and Scopus were searched through December 2025. Overall survival (OS) was the primary outcome; progression-free survival (PFS) and objective response rate (ORR) were secondary outcomes. Hazard ratios (HRs) and odds ratios (ORs) were pooled using random-effects models. Heterogeneity, publication bias, and meta-regression were assessed.
Results:
Twelve RCTs were included. Immunotherapy was associated with significantly worse OS compared with control (pooled HR = 1.16, 95% CI 1.06-1.28; I² = 14.2%). No OS benefit was observed in any individual trial. PFS (11 trials) showed no consistent improvement (pooled HR = 0.93, 95% CI 0.70-1.24; I² ≈ 78%), and ORR (OR = 1.17, 95% CI 0.91-1.51) demonstrated heterogeneous, non-survival-concordant signals driven by small studies. Meta-regression identified phase III trial status as the dominant predictor of unfavorable OS effects.
Conclusions:
Randomized trials demonstrate no improvement in overall survival with immunotherapy in glioblastoma, while signals in progression-free survival and objective response remain inconsistent and biased, with no survival concordance.
Insights
Immunotherapy offers no overall survival benefit for glioblastoma patients and may worsen outcomes. Progression-free survival and response rates show inconsistent, biased signals, highlighting the need for new treatment strategies.
Area of Science:
- Neuro-oncology
- Clinical immunology
- Biostatistics
Background:
- Immunotherapy has revolutionized solid tumor treatment but shows limited efficacy in glioblastoma.
- Prior early-phase trials suggested potential, but lacked translation into survival benefits in randomized studies.
- Uncertainty persists regarding the clinical value of immunotherapy for glioblastoma.
Purpose of the Study:
- To systematically evaluate the efficacy of immunotherapy in adult glioblastoma using a meta-analysis of randomized controlled trials (RCTs).
- To determine the impact of immunotherapy on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
Main Methods:
- A systematic review and random-effects meta-analysis of 12 RCTs were conducted.
- Searches included PubMed, Embase, and Scopus up to December 2025.
- Pooled hazard ratios (HRs) and odds ratios (ORs) were calculated, with heterogeneity and bias assessed.
Main Results:
- Immunotherapy was associated with significantly worse OS (HR = 1.16; 95% CI 1.06-1.28).
- PFS showed no consistent improvement (HR = 0.93; 95% CI 0.70-1.24) with substantial heterogeneity (I² ≈ 78%).
- ORR signals were heterogeneous and non-survival-concordant (OR = 1.17; 95% CI 0.91-1.51), influenced by small studies; Phase III trial status predicted worse OS.
Conclusions:
- Randomized trials confirm no OS improvement with immunotherapy in glioblastoma.
- Observed signals in PFS and ORR are inconsistent, potentially biased, and lack survival concordance.
- Current immunotherapy approaches demonstrate limited clinical value in glioblastoma.
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