Stupp and colleagues recently published a Phase III randomized trial of the NovoTTF-100A device (Novocure) versus physician’s choice chemotherapy in patients with recurrent GBM.3 For the study, 237 patients at 28 centers in seven countries were randomized to TTFields or active chemotherapy (treating with physician’s choice). Patients were required to have a diagnosis of supratentorial GBM with radiographic progression following radiation therapy. Concomitant/adjuvant temozolomide was not required. There was no limit on number or type of prior regimens, as long as patients had adequate hematologic, renal, and hepatic function. Patients randomly assigned to the NovoTTF-100A device were required to be connected to the device near continuously.
There was a high patient dropout in the treatment group (22%) due to difficulty with compliance or device management. In the 116 patients who started TTFields therapy, median compliance was 86%, corresponding to an average use of the device for 20.6 hours/day. Most of the chemotherapy patients completed at least one cycle of treatment, regardless of regimen. A wide variety of single-agent and combination regimens were used, including bevacizumab, irinotecan, temozolomide, other nitrosoureas, and carboplatin. Median survival was comparable in the two arms, as was 1-year survival. Overall, the NovoTTF-100A device was found to be noninferior to active chemotherapy, regardless of regimen chosen, with significantly reduced toxicity and improved quality of life.
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As a result of these studies, the FDA has approved the NovoTTF-100A device for use as monotherapy in patients with recurrent GBM. At the present time, less than 20 physicians across the United States have been trained to prescribe treatment with the device. The optimum patient for this treatment has reasonable performance status; is willing to comply with treatment, including biweekly head shaving and connection to the device for 20+ hours daily; has the ability to learn to apply electrodes (or a caregiver capable of the task); and is willing to use the device as monotherapy. The safety of the device in combination with chemotherapy has been suggested in a pilot trial, but is not yet ascertained. A Phase III randomized trial of NovoTTF-100A combined with standard chemoradiation versus standard therapy is underway at multiple sites across the United States and Europe.
The NovoTTF-100A device is a novel and safe treatment for recurrent GBM. It is not a panacea, but rather represents a different direction in tumor treatment that uses physics, not just chemistry, to disrupt cell growth. Despite the skepticism that has permeated the neuro-oncology community, it definitely warrants further investigation. Additional trials studying other tumor types are ongoing or being planned, and new devices to treat other body areas are in development. The oncology community should look out for new opportunities using this interesting therapy.
REFERENCES
1. Kirson ED, Gurvich Z, Schneiderman R, et al. Cancer Res. 2004;64(9):3288-3295.
2. Kirson ED, Dbalý V, Tovarys F, et al. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007:104(24):10152-10157.
3. Stupp R, Wong ET, Kanner AA, et al. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality [published online ahead of print May 18, 2012]. Eur J Cancer.
