Survival Improvement With NovoTTF Leads to Early End of Phase III Trial

November 16, 2014

Use of the NovoTTF system along with adjuvant temozolomide led to longer progression-free survival and overall survival in patients with glioblastoma.

Roger Stupp, MD

Use of the Novo Tumor Treating Fields (NovoTTF) system along with adjuvant temozolomide led to longer progression-free survival and overall survival in patients with glioblastoma, according to late-breaking results from a phase III trial presented at the Society for Neuro-Oncology (SNO) Annual Meeting.

“A new cancer treatment modality has been born,” said Roger Stupp, MD, the trial’s principal investigator, reporting the data from the EF-14 study, a prospective, multicenter, international trial of NovoTTF-100A in combination with temozolomide conducted across 83 sites in 12 countries. Stupp is a professor and chairman of the Department of Oncology, and director, University Hospital Cancer Center, at the University of Zurich in Switzerland.

NovoTTF, manufactured by Novocure, is a portable, noninvasive, battery-operated device which attaches to the patient’s head to deliver tumor treating fields to the brain. The NovoTTF appears to slow and reverse tumor growth by inhibiting mitosis. “It was shown in preclinical data that the device could inhibit tumor growth,” Stupp explained.

Patients use the system at home and may wear it as long as 20 to 22 hours a day. As manufacturers refine the device, it continues to get smaller, Stupp added. The NovoTTF-100A system is approved by the FDA to treat adults 22 and older with GBM that recurs or progresses after receiving chemotherapy and radiation therapy.

After receiving radiotherapy with concomitant temozolomide, the study’s 315 patients were randomized 2:1 to receive NovoTTF and temozolomide in combination (n = 210) or temozolomide alone (105 patients). The study’s primary endpoint was progression-free survival (PFS), and its secondary endpoint was overall survival (OS).

Eligibility criteria included pathologic evidence of glioblastoma using World Health Organization classification criteria, being aged 18 or older, having maximal debulking surgery and radiotherapy along with temozolomide, a Karnofsky performance status of 70% or higher, and a life expectancy of at least 3 months. Patients had to have used a stable or decreasing dose of steroids, and the interval since radiation therapy had to have been more than 29 days but fewer than 49 days.

Patient characteristics were similar in both groups, with an average age of 57 for the combination group and 58 for the temozolomide-only control arm. Tumor resection was 89% and 90%, respectively, and Karnofsky performance status was 90% in both groups. Of the 60% of patients who were assessable for MGMT promoter methylation status, 39% and 41% were methylated, respectively.

Median PFS was 7.1 months with the combination and 4 months in the temozolomide-only group (HR = 0.63; P = .001). OS was 19.6 months and 16.6 months, respectively (HR = 0.75; P = .034), and the 2-year survival rate was 43% and 29%, respectively.

“If you are a patient, [those numbers] are meaningful. If you are an investigator, you want more. However, it’s a step forward,” Stupp said. The results led to early termination of the trial, and all patients in the control arm were allowed to receive the combination.

Skin irritation occurred in 45% of patients. Severe seizures occurred at a frequency of 7% in both groups.

The data reported at the SNO meeting were after a minimum 18-month follow-up. Researchers had compiled and analyzed the data 4 weeks before the meeting, Stupp noted. Future research will evaluate quality of life and survival at 1 and 2 years.

Although researchers wondered if patients would feel anxious about using the device, Stupp said in his own clinical experience, patients actually feel motivated by it. “They feel like they’re doing something [to help themselves],” he said. “That was striking to me.”

Stupp R, Wong E, Scott C, et al. Interim analysis of the EF-14 trial: a prospective, multicenter trial of NovoTTF-100A together with temozolomide compared to temozolomide alone in patients with newly diagnosed GBM. Presented at: 19th Annual Meeting of the Society for Neuro-Oncology; November 13-16, 2014: Miami, FL.

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