Extended Dosing (12 Cycles) of Adjuvant Temozolomide in Adults with Newly Diagnosed High Grade Gliomas: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines

Question

1. What is the clinical effectiveness of extended dosing (12 cycles) of adjuvant temozolomide in adult patients with newly diagnosed high grade gliomas?
2. What is the cost-effectiveness of extended dosing (12 cycles) of adjuvant temozolomide in adult patients with newly diagnosed high grade gliomas?
3. What are the evidence-based guidelines associated with the use of adjuvant temozolomide in adult patients with newly diagnosed high grade gliomas?

Key Message

Evidence from two randomized controlled trials and one non-randomized controlled trial of adult patients with newly-diagnosed gliomas suggest that compared with the conventional 6-cycle adjuvant temozolomide therapy, the 12-cycle regimen was associated with improved survival outcomes, including overall survival and progression-free survival, although the between-group difference in overall survival was not statistically significant. The use of 12-cycle adjuvant temozolomide therapy was also related to higher risks of Grade 3-4 toxicities compared with the 6-cycle regimen, especially for hematological toxicities. However, the clinical effectiveness of extended dosing of adjuvant temozolomide relative to conventional 6-cycle regimen should be interpreted with caution, due to the compromised quality and the small sample size in some of the included trials. Two evidence-based clinical practice guidelines developed in Spain recommend the use of 12-cycle adjuvant temozolomide therapy after surgery and radiotherapy, for newly-diagnosed glioblastoma in elderly patients ( 65 years) or anaplastic astrocytoma.No relevant economic evaluations were identified from the literature to examine the cost-effectiveness of 12-cycle temozolomide therapy in the population of interest.