Temozolomide plus radiotherapy for glioblastoma in a Canadian province: efficacy versus effectiveness and the impact of O6-methylguanine-DNA-methyltransferase promoter methylation.

Background: Radiotherapy with concomitant and adjuvant temozolomide has been the standard of care for newly diagnosed glioblastoma in adults since the pivotal trial by Roger Stupp and colleagues. The effectiveness of this regimen has not been evaluated in Canada. Additionally, the impact of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation on patient survival has not been confirmed. Hence, survival outcomes and MGMT predictive value were compared for the patients in Alberta versus the Stupp trial population.
Methods: Retrospective chart review of 215 adult glioblastoma patients who started radiotherapy and temozolomide between January 2007 and December 2010 at the Cross Cancer Institute (Edmonton, Alberta) or the Tom Baker Cancer Centre (Calgary, Alberta).
Results: In the Alberta population, median overall survival was 14.3 months (vs. 14.6 months in trial, p = NS) and median progression-free survival was 5.8 months (vs. 6.9 months in trial, p = NS). However, unlike the trial, the Alberta MGMT subgroup analysis for overall survival was not statistically significant, despite a hazard ratio of 0.65 in favor of the methylated group. More Alberta patients received corticosteroids (p < 0.0001) and fewer underwent complete resection (p = 0.0001) or a postprogression second surgery (p = 0.01) than the Stupp population, but characteristics were otherwise similar.
Conclusion: Current practice in Alberta enables patients to achieve overall and progression-free survival similar to the clinical trial. Further follow-up is required to confirm the predictive value of the MGMT assay. Until that is clarified or better treatments are developed, it is reasonable to continue offering this treatment regimen to patients regardless of MGMT methylation status.