Original Title: Tumour treating fields (TTFields) per il trattamento di pazienti con nuova diagnosi o con recidiva di glioblastoma

Authors' objectives: To assess the clinical efficacy, safety, economic and organisational impact of introducing Tumour Treating Fields (Optune®) for the treatment of : (1) adult patients with newly diagnosed GBM until first progression; (2) adult patients with recurrent or progressive GBM

Authors' results and conclusions: Comparative clinical efficacy and safety in patients with newly diagnosed GBM: The evidence is based mainly on the results of a randomised clinical trial (EF-14). The EF-14 trial compared maintenance therapy with TTF+TMZ to maintenance therapy with TMZ alone, reporting efficacy estimates for OS (HR 0.63, 95% CI 0.53-0.76), for PFS (HR 0.63, 95% CI 0.52- 0.76) and safety estimates in terms of the occurrence of 1 or more severe adverse events (RR 1.10, 95% CI 0.92-1.31). Taking into account the results of the EF-14 trial and the relative certainty of the evidence, it can be concluded that, in the treatment of patients with newly diagnosed GBM, the use of TTF in addition to TMZ compared to maintenance TMZ alone may (possibly) be effective in terms of increasing overall survival and progression-free survival (low certainty of evidence). The effect on patient quality of life is estimated to be minimal or negligible, but the evidence is very uncertain (very low certainty of evidence). In terms of safety, the use of TTF in addition to TMZ compared to maintenance TMZ alone may (possibly) have a minimal or no effect on the frequency of serious adverse events (low certainty of evidence). Comparative clinical efficacy and safety in patients with recurrent or progressive GBM: The evidence is based mainly on the results of a randomised clinical trial (EF-11). The EF-11 trial compared TTF therapy alone with second-line chemotherapy, reporting efficacy estimates for OS (HR 0.86, 95% CI 0.66-1.12), for PFS (HR 0.81, 95% CI 0.60-1.09) and safety estimates in terms of the occurrence of 1 or more severe adverse events (RR 0.37, 95% CI 0.16-0.86). Taking into account the results of the EF-11 trial and the relative certainty of the evidence, it can be concluded that, in patients with recurrent or progressive GBM, treatment with TTF alone compared with second-line chemotherapy may result in little or no difference in terms of overall survival, progression-free survival and impact on quality of life, but the evidence is very uncertain (very low certainty of evidence). In terms of safety, treatment with TTF alone may result in fewer serious adverse events than treatment with second-line chemotherapy alone (very low certainty of evidence). Adverse events and medical device vigilance reports: The most frequently reported adverse events by TTF users are skin lesions (erythema, ulcerations, dermatitis) at the site of application of the device. The most frequent incident reports emerging from medical device vigilance databases relate to skin irritation, followed by headaches, falls, neurological disorders and epileptic seizures. Acceptability: The treatment requires high compliance to ensure its effectiveness and must be carried out for ≥18 hours per day. The literature indicates variable compliance and acceptability, both on the part of patients and professionals. No data on acceptability in an Italian context was found. Economic evaluation of cost-effectiveness and cost-utility: The analysis showed that the cost-effectiveness and cost-utility ratios were unfavourable compared to regional and national standards. Budget Impact: The estimated total increase in regional healthcare expenditure, considering various usage scenarios, ranges from €32,422,499 to €78,435,431 (including VAT) over a three-year period. Ethical and social aspects: Critical issues have been identified relating to equity in access, home care management and the high economic burden on the healthcare system

Authors' methods: The assessment included six domains covered by the EUnetHTA 3.0 Core Model. A systematic review of the literature was conducted, updating the research carried out in April 2023 as part of a previous HTA assessment with the same health policy questions to March 2025. The literature update identified four non-randomised comparative studies, which were added to the two RCTs and two non-randomised comparative studies already included in the previous HTA assessment. A full economic evaluation (cost-effectiveness, cost-utility) was conducted based on overall survival (OS), progression-free survival (PFS), quality-adjusted life year (QALY) estimates, and costs. A 3-year Budget Impact Analysis was also carried out, considering a monthly cost of €21,840.00 (including VAT) for the Optune Gio® device, based on data from the regional cancer registry. Alternative models were developed based on different clinical and economic use assumptions.

Project Status: Completed

Year Published: 2025

URL for published report: https://salute.regione.emilia-romagna.it/farmaci/dispositivi-medici/ttfields-optune-1.pdf/@@download/file/TTFields%20-%20Optune.pdf

Requestor: Commissione Regionale Dispositivi Medici (CRDM)

URL for additional information: https://salute.regione.emilia-romagna.it/farmaci/dispositivi-medici/centro-regionale-hta-dm

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Italy

Organisation Name: Regione Emilia Romagna

Contact Address: Viale Aldo Moro 21, 40127 Bologna, Italia

Contact Name: danilo.dilorenzo@regione.emilia-romagna.it

Contact Email: centro.HTADM@regione.emilia-romagna.it

Copyright: Regione Emilia-Romagna