Study findings support post-radiation clinical trial enrollment instead of temozolomide for unmethylated patients with glioblastoma, according to a study presented at the virtual 2021 ASCO Annual Meeting.

“Recently, several investigators have suggested the small survival benefit of temozolomide for unmethylated patients is insufficient to warrant the increased risk of adverse events and that these patients should instead be enrolled in clinical trials” wrote Mark Edward Votruba, PhD, Department of Economics, Case Western Reserve University, and Center for Health Care Research and Policy, Cleveland, OH, and colleagues, adding “This study informs the debate by estimating the incremental costs and benefits associated with [temozolomide] use in methylated and unmethylated patients based on available published evidence.”

Overall survival (OS) and progression-free survival (PFS) Kaplan-Meier curves were extrapolated to 10 years. Data including costs of temozolomide, radiation therapy, and inpatient hospitalization, were used to build a Partitioned Survival Analysis.

The analysis assumed all patients receive surgery prior to beginning radiation, and that radiation therapy and temozolomide dosing was standard. In addition, a 3% annual discount rate and a willingness-to-pay threshold of $150,000/quality-adjusted life year (QALY) were assumed. Probabilistic sensitivity analysis was performed.

Among methylated patients, radiation plus temozolomide was associated with $67,622 in additional costs and 10.91 additional quality-adjusted life months (QALMs) when compared to those receiving radiation therapy alone. Among unmethylated patients, radiation plus temozolomide was associated with $9,203 in additional costs and 2.24 additional QALMs, compared to unmethylated patients receiving radiation therapy alone.

While the implied incremental cost effectiveness ratios (ICER) suggest that temozolomide use is more favorable among unmethylated patients ($74,378/QALY for methylated patients vs $49,302/QALY for unmethylated patients), the incremental net monetary benefit suggests that due to the smaller survival gains, temozolomide use is substantially smaller among unmethylated patients ($18,797 vs $68,753).

Probabilistic sensitivity analysis found that temozolomide is more likely to be cost-effective for methylated patients than unmethylated patients (89.3% vs 77.4%, respectively).

“Post-radiation clinical trial enrollment should be considered instead of [temozolomide] for unmethylated glioblastoma patients” concluded Dr Votruba and colleagues, adding “While the estimated ICER justifies the use of [temozolomide] for unmethylated patients – in fact, does so more strongly than for methylated patients – the relatively small incremental health benefit is plausibly outweighed by the opportunity cost of not enrolling these patients in clinical trials that offer the possibility of more substantive gains to current and future glioblastoma patients.”—Marta Rybczynski

Midha MD, Votruba ME. Cost-effectiveness of concomitant and adjuvant temozolomide for glioblastoma patients with unmethylated O6-methylguanine-DNA methyltransferase promoter regions in the United States. Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 2058.