Background
Contemporary standard-of-care for newly-diagnosed glioblastoma (GBM) is maximal safe resection followed by post-operative focal conformal radiotherapy (RT) plus concurrent temozolomide (TMZ) and 6-cycles of adjuvant TMZ (Stupp regimen). However, many patients continue to receive extended adjuvant TMZ (beyond 6-cycles) without solid scientific evidence. This review pools data from non-randomized studies and randomized controlled trials (RCTs) comparing extended adjuvant TMZ (>6-cycles) to standard adjuvant TMZ (6-cycles) in patients with newly-diagnosed GBM for updated evidence-synthesis.
Methods
This systematic review and meta-analysis was carried out in accordance with the Cochrane methodology including quality assessment of primary studies. Primary outcome of interest was comparative efficacy defined as progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) for PFS and OS with corresponding 95% confidence interval (CIs) were extracted/computed from individual primary studies and pooled using random-effects model. Any p-value <0.05 was considered statistically significant.
Results
Evidence-synthesis was based on pooling of data from 2578 patients enrolled in 16 non-randomized comparative studies and 5 RCTs. Overall, extended adjuvant TMZ was associated with statistically significant reduction in the risk of progression (HR=0.72, 95%CI:0.60-0.87; p=0.007) and death (HR=0.71, 95%CI:0.57-0.90; p=0.004) compared to standard adjuvant TMZ. However, on subgroup analysis, survival benefit of extended adjuvant TMZ was limited to data synthesized from retrospective non-randomized comparative studies with no statistically significant difference in outcomes seen after pooling of data from RCTs only.
Conclusion
Apparent survival benefit of extended adjuvant TMZ in newly-diagnosed GBM is largely driven by non-randomized comparative studies with high inherent potential for multiple biases.