Cost-effectiveness of concomitant and adjuvant temozolomide for glioblastoma patients with unmethylated O6-methylguanine-DNA methyltransferase promoter regions in the United States.

Abstract

2058 Background: Promoter region methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene has emerged as a predictive factor for longer overall (OS) and progression-free (PFS) survival response to concomitant and adjuvant temozolomide (TMZ) chemotherapy in glioblastoma. Recently, several investigators have suggested the small survival benefit of TMZ for unmethylated patients is insufficient to warrant the increased risk of adverse events and that these patients should instead be enrolled in clinical trials. This study informs the debate by estimating the incremental costs and benefits associated with TMZ use in methylated and unmethylated patients based on available published evidence. Methods: Published OS and PFS Kaplan-Meier curves were digitized, parameterized, and extrapolated to ten years. Partitioned Survival Analysis trees were constructed in TreeAge Pro 2020. Costs of TMZ, RT, and inpatient hospitalization were included, among others. It was assumed that all patients receive surgery prior to beginning radiation, and that RT and TMZ (six adjuvant cycles) dosing was standard. Published utilities associated with the progression-free and post-progression health states, subject to each treatment, were used. A 3% annual discount rate and a willingness-to-pay of $150,000/quality-adjusted life year (QALY) were assumed. Probabilistic sensitivity analysis (PSA) was conducted. Results: In methylated patients, RT + TMZ versus RT is associated with $67,622 in additional costs and 10.91 additional quality-adjusted life months (QALMs). In unmethylated patients, RT + TMZ versus RT is associated with $9,203 in additional costs and 2.24 additional QALMs. The implied incremental cost effectiveness ratios (ICERs) support TMZ use in both populations and suggest it is more favorable for unmethylated patients ($74,378/QALY and $49,302/QALY for methylated and unmethylated patients, respectively). However, the incremental net monetary benefit (INMB) associated with TMZ use is substantially smaller for unmethylated patients ($18,797 versus $68,753) due to the smaller survival gains for this population. PSA results indicate that TMZ is more likely to be cost-effective for methylated (89.3%) than unmethylated (77.4%) patients. Conclusions: Post-radiation clinical trial enrollment should be considered instead of TMZ for unmethylated glioblastoma patients. While the estimated ICER justifies the use of TMZ 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.