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Review
. 2020 Oct 30;2(1):vdaa082.
doi: 10.1093/noajnl/vdaa082. eCollection 2020 Jan-Dec.

Characterizing benefit from temozolomide in MGMT promoter unmethylated and methylated glioblastoma: a systematic review and meta-analysis

Iyad Alnahhas  1 , Mouaz Alsawas  2 , Appaji Rayi  3 , Joshua D Palmer  4 , Raju Raval  4 , Shirley Ong  3 , Pierre Giglio  3 , Mohammad Hassan Murad  2 , Vinay Puduvalli  3
Affiliations
Review

Characterizing benefit from temozolomide in MGMT promoter unmethylated and methylated glioblastoma: a systematic review and meta-analysis

Iyad Alnahhas et al. Neurooncol Adv. .

Erratum in

Abstract

Background: The current standard of care for the management of patients with newly diagnosed glioblastoma (GBM) includes maximal safe resection followed by radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). While it is well established that TMZ has better efficacy in patients with MGMT promoter methylation, it remains an area of debate whether TMZ should be omitted when treating GBM patients with unmethylated MGMT.

Methods: We conducted a systematic review and meta-analysis to provide separate estimates of median overall survival (OS) and progression-free survival (PFS) for patients with methylated and unmethylated GBM treated with RT with or without TMZ. We searched multiple databases from inception to January 13, 2020.

Results: The median OS for patients with unmethylated GBM treated with RT/TMZ pooled from 5 phase III studies (N = 655) was 14.11 months (95% confidence interval [CI], 13.18-15.04) with a median PFS of 4.99 months (95% CI, 4.25-5.72). In contrast, the median OS for patients with methylated GBM pooled from 6 studies (N = 753) was 24.59 months (95% CI, 22.19-26.99) with a median PFS pooled from 7 studies (N = 805) of 9.51 months (95% CI, 7.41-11.61). There is a paucity of prospective data pertaining to OS/PFS in unmethylated patients treated with RT only and therefore a direct comparison was not possible.

Conclusions: This meta-analysis provides estimates of survival for patients with MGMT methylated or unmethylated GBM treated with RT/TMZ. Further research is needed to delineate whether TMZ should be withheld for patients with unmethylated GBM outside of the setting of clinical trials.

Keywords: MGMT; glioblastoma; meta-analysis; systematic review; temozolomide.

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Figures

Figure 1.
Figure 1.
PRISMA flow diagram of study inclusion and exclusion. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses.
Figure 2.
Figure 2.
Risk of bias assessment for studies included in the meta-analysis.
Figure 3.
Figure 3.
Forest plot showing pooled OS for patients with unmethylated GBM.
Figure 4.
Figure 4.
Forest plot showing pooled PFS for patients with unmethylated GBM.
Figure 5.
Figure 5.
Forest plot showing pooled OS or patients with methylated GBM.
Figure 6.
Figure 6.
Forest plot showing pooled PFS for patients with methylated GBM.
See this image and copyright information in PMC

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