Estimated Increase in Mean Lifetime Survival for Glioblastoma Patients Age 65 Years and Older Treated with Tumor Treating Fields and Temozolomide Compared to Patients Treated with Temozolomide Alone

Abstract

Tumor treating fields (TTFields) is a device-delivered treatment for glioblastoma (GBM) brain tumors. Post-hoc analysis of the EF-14 Trial demonstrated that the subgroup of patients age 65 or older obtained the greatest survival beneft from TTFields compared to temozolomide (TMZ) alone (HR = 0.51). The final analysis of the EF-14 Trial reported that for the subgroup of patients older than age 65, 5-year overall survival was 15% for patients treated with TTFields and maintenance TMZ, compared to no survivors in the TMZ alone arm. The objective of this analysis was to estimate the mean lifetime survival benefit of TTFields treatment for patients age 65 or older with newly diagnosed GBM. We constructed an integrated survival model that incorporated subgroup data for patients age 65 or older from the EF-14 Trial with epidemiological data on long-term GBM survival. We perfomed a literature search in the Medline database to identify epidemiological data to estimate survival in this age subgroup after the 5-year trial period. A discount rate of 3% was applied to future survival benefits. We also perfomed one-way and probabilistic sensitivity analyses and compared the results of our integrated survival model to regression based extrapolations of the trial data. Patients in this subgroup treated with TTFields and TMZ achieved an undiscounted mean lifetime survival of 3.8 years compared to 1.3 years for patients treated with TMZ alone. The resulting increase in mean lifetime survival after applying the discount rate to future health benefits was 1.8 years. Survival was 10% at 10-years and 8% at 15-years for patients treated with TTFields and TMZ. The results were most sensitive to uncertainty in long-term conditional survival estimates. This analysis of the subgroup of patients age 65 and older in the EF-14 trial demonstrated that treatment with TTFields and maintenance TMZ produced a notable increase in mean lifetime survival compared to treatment with TMZ alone. The lifetime survival benefit was achieved despite the relatively advanced age of the subgroup, reflecting the substantial survival benefit observed in the trial. The results of this analysis can inform future evaluations of the cost-effectiveness of TTFields for older patients with newly diagnosed GBM.