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Review
. 2021 Apr 9;3(1):vdab052.
doi: 10.1093/noajnl/vdab052. eCollection 2021 Jan-Dec.

Systematic review and network meta-analysis of the efficacy of existing treatments for patients with recurrent glioblastoma

Anna Schritz  1 , Nassera Aouali  2 , Aurélie Fischer  2 , Coralie Dessenne  3 , Roisin Adams  4 , Guy Berchem  5   6 , Laetitia Huiart  3 , Susanne Schmitz  1
Affiliations
Review

Systematic review and network meta-analysis of the efficacy of existing treatments for patients with recurrent glioblastoma

Anna Schritz et al. Neurooncol Adv. .

Abstract

Background: Despite advances in the treatment of cancers over the last years, treatment options for patients with recurrent glioblastoma (rGBM) remain limited with poor outcomes. Many regimens have been investigated in clinical trials; however, there is a lack of knowledge on comparative effectiveness. The aim of this systematic review is to provide an overview of existing treatment strategies and to estimate the relative efficacy of these regimens in terms of progression-free survival (PFS) and overall survival (OS).

Methods: We conducted a systematic review to identify randomized controlled trials (RCTs) investigating any treatment regimen in adult patients suffering from rGBM. Connected studies reporting at least one of our primary outcomes were included in a Bayesian network meta-analysis (NMA) estimating relative treatment effects.

Results: Forty RCTs fulfilled our inclusion criteria evaluating the efficacy of 38 drugs as mono- or combination therapy. Median OS ranged from 2.9 to 18.3 months; median PFS ranged from 0.7 to 6 months. We performed an NMA including 24 treatments that were connected within a large evidence network. Our NMA indicated improvement in PFS with most bevacizumab (BV)-based regimens compared to other regimens. We did not find any differences in OS between treatments.

Conclusion: This systematic review provides a comprehensive overview of existing treatment options for rGBM. The NMA provides relative effects for many of these treatment regimens, which have not been directly compared in RCTs. Overall, outcomes for patients with rGBM remain poor across all treatment options, highlighting the need for innovative treatment options.

Keywords: network meta-analysis; overall survival; progression-free survival; recurrent glioblastoma; systematic review.

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Figures

Figure 1.
Figure 1.
Flowchart of study selection.
Figure 2.
Figure 2.
Forest plot showing trial level outcomes of overall survival. BSC, Best supportive care; CBP, cannabidiol; THC, delta-9-tetrahydrocannabinol; PPV, personal peptide vaccination.
Figure 3.
Figure 3.
Forest plot showing trial level outcomes of progression-free survival. BSC, Best supportive care; CBP, cannabidiol; THC, delta-9-tetrahydrocannabinol; PPV, personal peptide vaccination.
Figure 4.
Figure 4.
Network graph for (A) overall survival and (B) progression-free survival. Nodes indicate treatment regimen, connections between nodes indicate direct evidence comparing adjacent treatments. ALE: Alecsat, BV: Bevacizumab, CBP: Carboplatin, CCNU: Carmustine, CDR: Cediranib, CPT-11: Irinotecan, DST: Dasatinib, ENZA: Enzastaurin, EPS: Etoposide, FTM: Fotemustine, GAL: Galunisertib, GFT: Gefitinib, NIVO: Nivolumab, Onar: Onartuzumab, Rego: Regorafenib, TMZ: Temozolomide, VRS:Vorinostat.
Figure 5.
Figure 5.
Hazard ratios (HR) of treatment comparisons versus bevacizumab. (A) For overall survival, (B) for progression-free survival. ALE: Alecsat, BV: Bevacizumab, CBP: Carboplatin, CCNU: Carmustine, CDR: Cediranib, CPT-11: Irinotecan, DST: Dasatinib, ENZA: Enzastaurin, EPS: Etoposide, FTM: Fotemustine, GAL: Galunisertib, GFT: Gefitinib, NIVO: Nivolumab, Onar: Onartuzumab, Rego: Regorafenib, TMZ: Temozolomide, VRS:Vorinostat.
Figure 6.
Figure 6.
The surface under the cumulative ranking curve (SUCRA) ranking score. Higher scores indicate higher ranked treatments. (A) Overall survival and (B) progression-free survival. ALE: Alecsat, BV: Bevacizumab, CBP: Carboplatin, CCNU: Carmustine, CDR: Cediranib, CPT-11: Irinotecan, DST: Dasatinib, ENZA: Enzastaurin, EPS: Etoposide, FTM: Fotemustine, GAL: Galunisertib, GFT: Gefitinib, NIVO: Nivolumab, Onar: Onartuzumab, Rego: Regorafenib, TMZ: Temozolomide, VRS: Vorinostat.
Figure 7.
Figure 7.
Risk of bias summary.
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