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

Nov 5, 2020Neuro-oncology advances

Temozolomide benefits in glioblastoma with and without MGMT gene methylation: a systematic review and meta-analysis

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Abstract

The median for patients with unmethylated glioblastoma treated with radiotherapy and temozolomide is 14.11 months.

Patients with unmethylated glioblastoma have a median of 4.99 months when treated with radiotherapy and temozolomide.
In contrast, patients with methylated glioblastoma have a median overall survival of 24.59 months and a median progression-free survival of 9.51 months.
Data on overall survival and progression-free survival for unmethylated patients treated with radiotherapy alone is limited.
This analysis indicates substantial differences in survival outcomes between patients with methylated and unmethylated glioblastoma treated with the same regimen.

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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 withpromoter methylation, it remains an area of debate whether TMZ should be omitted when treating GBM patients with unmethylated. MGMT MGMT

METHODS: We conducted a systematic review and meta-analysis to provide separate estimates of median (OS) and (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 (= 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 (= 753) was 24.59 months (95% CI, 22.19-26.99) with a median PFS pooled from 7 studies (= 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. N N N

CONCLUSIONS: This meta-analysis provides estimates of survival for patients withmethylated 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. MGMT

Key numbers

14.11 months

Median for unmethylated GBM

Pooled from 5 phase III studies involving 655 patients.

24.59 months

Median for methylated GBM

Pooled from 6 studies involving 753 patients.

4.99 months

Median for unmethylated GBM

Pooled from 5 phase III studies involving 655 patients.

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

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