Treatment With Tumour-Treating Fields Prolongs Glioblastoma Survival

Phase III trial findings support the use of tumour-treating fields delivered in conjunction with temozolomide in glioblastoma patients who completed chemoradiotherapy

medwireNews: Addition of tumour-treating fields (TTFields) to maintenance temozolomide therapy significantly extends progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma, show the interim results of a phase III trial.

As the trial met the predefined criteria for success, the independent data and safety monitoring committee “recommended study termination, thus allowing patients in the control group to crossover and receive TTFields”, say the researchers.

They explain that TTFields are a locoregionally delivered therapy that disrupts cell mitosis “by delivering low-intensity, intermediate-frequency (200 kHz) alternating electric fields”, and in preclinical studies, TTFields plus chemotherapy have shown a synergistic antitumour effect.

A total of 695 patients with supratentorial glioblastoma who were progression free after standard chemoradiation therapy were randomly assigned to receive maintenance temozolomide 150–200 mg/m2 per day for 5 days of each 28-day cycle either with or without TTFields. Treatment with the latter was “delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device”, the team writes in JAMA.

In the interim analysis, conducted after the first 315 randomised patients had been followed up for at least 18.0 months, median PFS was 7.1 months for the 210 patients randomly assigned to receive TTFields plus temozolomide. This was significantly longer than the 4.0 months recorded for the 105 patients given temozolomide alone, with a hazard ratio (HR) of 0.62.

The powered secondary endpoint of OS – assessed in the per-protocol population – was also significantly longer for the TTFields treatment arm (n=196) than for the temozolomide monotherapy arm (n=84), at 20.5 versus 15.6 months and an HR of 0.64. The study authors also observed an OS benefit in a “more conservative analysis” using the intention-to-treat population (19.6 vs 16.6 months).

And survival at 2 years from enrolment was 43% for patients treated with TTFields and temozolomide and 29% for those given only temozolomide, a significant difference.

As TTFields is delivered locally, “an increase in systemic adverse events was neither seen nor expected”, say Roger Stupp, from University Hospital Zurich in Switzerland, and colleagues. However, nearly half the patients in the TTFields group experienced grade 1 or 2 scalp irritation while grade 3 localised skin reactions occurred in 2% of TTFields-treated participants.

John Sampson, from Duke University in Durham, North Carolina, USA, writes in a related editorial that although the survival improvement is not as great as in the previous pilot study, the trial is “the first in a decade to demonstrate an improvement in survival in this disease.”

However, highlighting the limitations of the study design – such as the lack of a placebo control and treatment disparities between groups (median of six vs four cycles of temozolomide in the TTFields compared with the temozolomide alone arm) – he comments that “doubts may remain as to the true efficacy of this therapy”.

The editorialist concludes: “So, if TTFields therapy fails to be adopted, will this decision be attributed to professional parochialism or to data that are not trusted? The current study provides additional important data on a novel device for the treatment of glioblastoma, but it will not completely resolve that debate.”


Stupp R, Taillibert S, Kanner AA, et al.Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma.JAMA 2015; 314: 2535–2543. Advance online publication 15 December. doi:10.1001/jama.2015.16669

Sampson JH. Alternating Electric Fields for the Treatment of Glioblastoma. JAMA 2015; 314: 2511–2513. Advance online publication 15 December. doi:10.1001/jama.2015.16701

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