Addition of Tumor-Treating Fields to Maintenance Temozolomide in Glioblastoma
Final results of a phase III trial reported by Stupp and colleagues in JAMA indicate that adding antimitotic treatment with tumor-treating fields to maintenance temozolomide is associated with improved progression-free and overall survival in patients with previously treated glioblastoma. The tumor-treating fields modality interferes with glioblastoma cell division and organelle assembly by delivery of low-intensity alternating electric fields to the tumor.
Study Details
In this open-label trial, 695 patients from 83 sites in North America, Europe, the Republic of Korea, and Israel were randomized 2:1 between July 2009 and July 2014 to receive tumor-treating fields plus maintenance temozolomide (n = 466) or temozolomide alone (n = 229). Patients had to have undergone resection or biopsy, in addition to having completed chemoradiotherapy.
Tumor-treating fields treatment consisted of low-intensity, 200-kHz frequency, alternating electric fields delivered ≥ 18 h/d via a portable device connected to transducer arrays on the shaved scalp. Temozolomide treatment consisted of 150 to 200 mg/m2 for 5 days in 28-day cycles for 6 to 12 cycles.
The primary endpoint was progression-free survival in the intent-to-treat population. Patients had a median age of 56 years, 68% were male, 89% were white, and 49% were from the United States.
Survival Outcomes
A preplanned interim analysis reported in 2015 including the first 315 randomized patients showed improved progression-free and overall survival in the tumor-treating fields group. For the current report, patients were followed through December 2016. The median duration of tumor-treating fields treatment was 8.2 months.
Median follow-up was 40 months and minimum follow-up was 24 months. Median progression-free survival was 6.7 months in the tumor-treating fields group vs 4.0 months in the temozolomide-alone group (hazard ratio [HR] = 0.63, P < .001). Median overall survival was 20.9 vs 16.0 months (HR = 0.63, P < .001) in the two groups, respectively. In exploratory analysis, overall survival was 43% vs 31% at 2 years, 26% vs 16% at 3 years, and 13% vs 5% at 5 years.
Adverse Events
Grade 3 or 4 systemic adverse events occurred in 48% of patients in the tumor-treating fields group and 44% of the temozolomide-alone group, with the most common being nervous system disorders (24% vs 20%, seizure in 6% vs 6%), and blood and lymphatic system disorders (13% vs 11%, thrombocytopenia in 9% vs 5%). Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of the tumor-treating fields group.
The investigators concluded, “In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of [tumor-treating fields] to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis.”
The study was funded by Novocure Ltd.
Roger Stupp, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, is the corresponding author for the JAMA article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
