TTFields therapy was delivered continuously (ie, >18 hours/day) via 4 transducer arrays affixed to the shaved scalp of the patient and connected to a portable device. The temozolomide dosage was 150 to 200 mg/m2/d for 5 days of each 28-day cycle for 6 to 12 cycles. Patients underwent routine laboratory examinations on a monthly basis, and quality of life was assessed every 3 months. Magnetic resonance imaging also was routinely performed until radiological progression occurred, and adverse events were documented according to the National Cancer Institute’s Common Terminology Criteria (version 3.0) until 2 months after treatment discontinuation.

The trial was terminated when the interim analysis showed that patients receiving combination therapy had a survival advantage over those receiving temozolomide alone. The interim analysis included 210 patients in the TTFields plus temozolomide group and 105 patients in the temozolomide-only group. Median progression-free survival for this intention-to-treat population was 7.1 months for the combination group and 4.0 months for the monotherapy group (P=.001). Median overall survival was 19.6 months vs 16.6 months (P = .03), with the difference being more pronounced when the per-protocol population was examined: the median was 20.5 months in the TTFields plus temozolomide group (n=196) and 15.6 months in the temozolomide-only group (n= 84; P = .004).


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Whereas only 29% of patients in the temozolomide-only group were still alive 2 years post-enrollment, 43% of patients in the combination therapy group were—a statistically significant difference (P = .006). Further, no increase in systemic toxic effects was seen among patients receiving TTFields; however, more patients reported scalp irritation and also were more apt to complain of anxiety, confusion, insomnia, and headaches after initial exposure.

The addition of TTFields to temozolomide maintenance therapy presents a new standard of care that all patients should be offered following standard chemoradiotherapy, according to Professor Stupp. “But we are only at the beginning of a new era,” he said. “We need to understand which patients will most benefit from this treatment and why some patients fail. This will allow for further treatment optimization of malignant brain tumors.”

Further study is warranted, including efforts to continue to elucidate the mechanism of action of and resistance to TTFields. Nevertheless, this study stands out as the first in at least a decade to demonstrate a means to an improvement in survival in patients with glioblastoma.

“This study is the first to demonstrate that this noninvasive treatment delivers effective locoregional antitumor therapy,” said Professor Stupp. “With this proof-of-concept study we will now investigate the efficacy of this treatment in other cancer types. The study should also encourage investigators to pursue novel, out-of-the box approaches to cancer therapy,” he said.

References

  1. Stupp R, Taillibert S, Kanner AA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma a randomized clinical trial. JAMA. 2015;314(23):2535-254 
  2. Stupp R, Hegi HE, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459-466.