Estimated lifetime survival benefit of tumor treating fields and temozolomide for newly diagnosed glioblastoma patients

Abstract

Aim:To estimate the mean lifetime survival benefit, an essential component of health economic evaluations in oncology, of adding tumor treating fields (TTFields) to maintenance temozolomide (TMZ) for newly diagnosed glioblastoma patients.Methods:We integrated EF-14 trial data with glioblastoma epidemiology data. The model provided for an evidence-based approach to estimate lifetime survival for the material number of EF-14 trial patients still alive at 5 years.Results & conclusion:Patients treated with TTFields and TMZ had an incremental mean lifetime survival of 1.8 years (TTFields/TMZ: 4.2 vs TMZ alone: 2.4). Patients alive at year 2 after starting TTFields had a 20.7% probability of surviving to year 10. The results presented here provide the required incremental survival benefit necessary for a future assessment of the incremental cost–effectiveness of TTFields.

Tumor treating fields and maintenance temozolomide for newly-diagnosed glioblastoma: a cost-effectiveness study

“…Bernard-Arnoux et al 39 estimated GBM survival using exponential extrapolation of median EF-14 survival rates. We previously observed this approach to be a poor visual fit to the actual EF-14 K-M survival curves, and that the exponential extrapolation had the worst fit of four estimated parametric approaches according to Akaike's information criterion testing 19 ; the Bernard-Arnoux et al 39 study consequently estimated that the TTFields and TMZ arm and TMZ alone arm converged by year-5, which was not observed in the trial.…”

“…Our literature review of long-term GBM OS has been described previously 19 . Given the material number of 5-year survivors in the EF-14 trial, we reviewed epidemiological literature reporting long-term GBM survival to determine the best modeling approach to extrapolate the EF-14 survival curves.…”

“…Upon review 19 , we concluded that the introduction of TMZ in 2005 was potentially a confounding factor for estimating survival beyond 5 years in the remaining three studies, as they included pre-and post-2005 populations 7,20,21 . Therefore, we selected the study by Porter et al 7 , which was based on 5,991 GBM patients in the National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) registries, to model long-term overall survival due to its homogeneous population of pre-TMZ patients, long-term data horizon, and data maturity.…”

“…We fit several parametric functions to the EF-14 trial PFS and OS Kaplan-Meier data; our approach to modeling long-term OS for EF-14 trial patients has been described previously 19 . The fitted distributions included exponential, Weibull, loglogistic, and log-normal.…”

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“…However, due to relatively small numbers of 3-year survivors, a 3-year survival rate could not be estimated reliably for TTFields-treated patients [99]. Integrating EF-14 trial data with glioblastoma epidemiology data, Guzauskas et al estimated the conditional survival rates at 3, 5, 10, and 15 years for the EF-14 trial patients alive at year 2 [100]. The authors concluded that patients alive at year 2 after starting TTFields with adjuvant TMZ had 59.6%, 29.4%, 20.7%, and 17.4% probability of surviving to year 3, 5, 10, and 15 versus 53.1%, 14.7%, 10.3%, and 8.7% probability of surviving for patients alive at year 2 after starting maintenance TMZ only [100].…”