Tumor treating fields (TTFields): A novel treatment modality added to standard chemo- and radiotherapy in newly diagnosed glioblastoma—First report of the full dataset of the EF14 randomized phase III trial.

2000 Background: TTFields is an established antimitotic treatment modality delivered to patients by a portable, home use, medical device. Here we evaluate whether this antimitotic effect can be translated into improved survival in a clinical setting. Based on a pre-specified interim analysis on 315 patients, the IDMC recommended early trial closure; we here report the first analysis of the full dataset of 700 randomized patients. Methods: This prospective phase 3 trial randomized patients with newly diagnosed glioblastoma, after completion of concomitant chemoradiotherapy, to receive either adjuvant temozolomide (TMZ) chemotherapy alone, or TMZ with TTFields (TTF/TMZ). The primary endpoint was progression-free survival, with overall survival, safety, cognitive function and quality of life as secondary endpoints. Results: (ITT) From 2009 to 2014, 700 Grade IV astrocytoma (glioblastoma) patients (68% male) were randomized 2:1. Patient characteristics were well balanced: median age was 56 and 57 years in the TMZ and TTF/TMZ arms, respectively. Tumor was resected in 87% of patients. MGMT was centrally assessed in 77% of patients, 35% and 39% of the tumors had a methylated promoter; 10% and 8% of the results were invalid. Median time from diagnosis to randomization was 3.8 and 3.7 months. Progression-free survival was 7.1 for TTF/TMZ vs 4.2 months for TMZ alone, hazard ratio (HR) 0.694 (95% CI 0.558-0.863) log rank p = 0.0010; overall survival 19.4 vs 16.6 months, HR 0.754 (0.595-0.955), p = 0.0222. This translates into 2-year survival rates of 43% (CI 36-50%) vs. 29% (CI 21-38%). No significant added toxicity was seen in the TMZ/TTF arm. Quality of life and gross cognitive function were comparable in the 2 arms. Conclusions: This is the first randomized trial demonstrating improved progression-free and overall survival of patients treated with Tumor Treating Fields. It sets a new standard of care for patients with glioblastoma, and warrants further investigation in other clinical indications. Clinical trial information: NCT00916409.