Background This study was designed to compare outcomes of extended adjuvant temozolomide (TMZ) versus standard adjuvant TMZ following radiotherapy (RT) plus concurrent TMZ in newly-diagnosed glioblastoma. Methods This systematic review and meta-analysis was carried out in accordance with Cochrane methodology. Only prospective clinical trials randomly assigning adults with newly-diagnosed glioblastoma after concurrent RT/TMZ to 6-cycles of adjuvant TMZ (control arm) or extended (>6-cycles) adjuvant TMZ (experimental arm) were eligible. Primary outcome of interest was overall survival, while progression-free survival and toxicity were secondary endpoints. Hazard ratio (HR) for progression and death with corresponding 95% confidence interval (CI) were computed for individual primary study and pooled using random-effects model. Toxicity was defined as proportion of patients with ≥grade 3 hematologic toxicity and expressed as risk ratio (RR) with 95%CI. Any p-value <0.05 was considered statistically significant. Results Systematic literature review identified five randomized controlled trials comparing standard (6-cycles) versus extended (>6-cycles) adjuvant TMZ in newly-diagnosed glioblastoma. Outcome data could be extracted from 358 patients from four primary studies. Extended adjuvant TMZ was not associated with statistically significant reduction in the risk of progression (HR=0.82, 95%CI: 0.61-1.10; p=0.18) or death (HR=0.87, 95%CI:0.60-1.27; p=0.48) compared to standard adjuvant TMZ. Grade ≥3 hematologic toxicity though somewhat higher with extended adjuvant TMZ, was not significantly different between the two arms (RR=2.01, 95%CI: 0.83-4.87; p=0.12). Conclusions There is low-certainty evidence that extended adjuvant TMZ is not associated with significant survival benefit or increased hematologic toxicity in unselected patients with newly-diagnosed glioblastoma compared to standard adjuvant TMZ.

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