MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma
- Study type
- Observational study
- Study name
- MGMT-Hegi
- Design
- Biomarker subgroup analysis of a randomised trial (comparing radiotherapy alone with radiotherapy plus concomitant and adjuvant temozolomide)
- Sample size
- 206 evaluable cases
- Source
- N Engl J Med · 2005
In plain words
In some patients with glioblastoma (a malignant brain tumour), a gene called MGMT, which helps repair DNA damage, is "switched off". This research showed that patients whose tumour has this feature benefit more from the drug temozolomide given with radiotherapy and live longer. In patients whose tumour did not have this gene switched off, no benefit from the drug was seen, or the benefit was smaller and not significant.
Key results
Treatment arms and regimens
Focal radiotherapy 60 Gy: 2 Gy daily, 5 days a week, for 6 weeks (30 fractions).
Focal radiotherapy 60 Gy: 2 Gy daily, 5 days a week, for 6 weeks (30 fractions).
Concomitant temozolomide: 75 mg/m² orally daily, 7 days a week, from the first to the last day of radiotherapy; then, after a 4-week break, 6 cycles of adjuvant temozolomide 150 to 200 mg/m² for 5 days in each 28-day cycle.
Source of the regimen details: Regimen of the parent EORTC-NCIC trial (Stupp et al., NEJM 2005, PubMed 15758009; doses in the abstract) and the FDA label for temozolomide (4-week interval before maintenance)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with glioblastoma enrolled in a randomised trial comparing radiotherapy alone with radiotherapy plus concomitant and adjuvant temozolomide whose tumour sample could be assessed for MGMT promoter methylation status (206 cases).
Endpoints
The association between MGMT gene silencing in the tumour (determined by promoter methylation status using methylation-specific polymerase chain reaction) and patient survival, and the benefit of temozolomide by methylation status.
Safety and side effects
Safety data are not reported in the abstract.
Clinical significance and place in guidelines
Based on the abstract, MGMT promoter methylation status is both an independent favourable prognostic factor and associated with benefit from temozolomide. This finding shows the importance of MGMT testing in glioblastoma. The current place of this test in treatment decisions and clinical guidelines should be checked in up-to-date sources.
Limitations
This is a biomarker analysis of 206 evaluable cases from the parent trial. In the unmethylated group, the survival difference was small and not significant. Other limitations are not mentioned in the abstract and should be checked in the full text of the paper.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.