NT-40 * Interim Analysis of the EF-14 Trial: A Prospective, Multi-center Trial of NovoTTF-100A Together With Temozolomide Compared to Temozolomide Alone in Patients with Newly Diagnosed GBM

Abstract

BACKGROUND: Tumor Treating Fields (TTFields) are an anti-mitotic, physical treatment modality that acts in metaphase, anaphase and telophase. The NovoTTF-100A System (NovoTTF), a home-use medical device that delivers TTFields to the brain, is an established monotherapy for recurrent glioblastoma (GBM). METHODS: We conducted an international, multicenter, prospective, randomized phase III trial in newly diagnosed GBM patients. After completion of radiotherapy (RT) with concomitant temozolomide (TMZ), patients were randomized (2:1) to adjuvant TMZ with NovoTTF or adjuvant TMZ alone. The primary endpoint was progression-free survival (PFS), with overall survival (OS) an important secondary endpoint. Here we report on a pre-specified interim analysis of the first 315 patients randomized, after a minimum follow-up of 18 months (range 18-60 months). RESULTS: (intent-to-treat): 210 pts were randomized to NovoTTF/TMZ and 105 to TMZ alone. Patient characteristics were balanced: median age 57 and 58 years, tumor resection in 89 and 90%, KPS 90%, for the NovoTTF and the control arms, respectively. MGMT promoter methylation status was assessable centrally in 60% of patients; of these 39% and 41% were methylated. Adverse events (AE) were comparable between treatment arms. The most common device-related AE was skin irritation in 45% of patients (all grades, severe 2%). Severe seizures were observed at a frequency of 7% in both arms. Median PFS was 7.1 months [mo] (95% confidence interval [CI] 5.9-8.2) and 4.0 mo (CI 3.0-4.3; Hazard ratio 0.63, p = 0.001), OS was 19.6 mo (CI 16.5.-24.1) and 16.6 mo (CI 13.5-19.1) (HR 0.75, p = 0.034), both favoring NovoTTF. This translates into a 24-mo survival rate of 43% (CI 36-50%) and 29% (CI 21-39%) for the NovoTFF/TMZ and the TMZ alone arm, respectively. CONCLUSIONS: The trial met its primary and main secondary endpoints, and was closed to accrual after this interim analysis. Adjuvant TMZ chemotherapy and NovoTTF provides a clinically and statistically significant improvement in progression-free and overall survival, and should become the new standard of care against GBM. View this table: NOU265TB1500400NOU265TB1 Top 10 recruiters - absolute numbers - global: View this table: NOU000TB2500400NOU000TB2 Top 10 recruiters - patients/month - global: