Addition of Tumor-Treating Fields to Maintenance Temozolomide in Glioblastoma

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Roger Stupp, MD

Roger Stupp, MD

The final results of a phase III trial reported by Roger Stupp, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 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. 

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. The median age of patients was 56 years, 68% were male, 89% were white, and 49% were from the United States. 

A preplanned interim analysis reported in 2015 including the first 315 randomized patients showed improved progression-free and overall survival with tumor-treating fields. 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 with tumor-treating fields vs 4.0 months with temozolomide alone (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 an exploratory analysis, overall survival was 43% vs 31% at 2 years, 26% vs 16% at 3 years, and 13% vs 5% at 5 years. 

Grade 3 or 4 systemic adverse events occurred in 48% of patients who received the tumor-treating fields and 44% of those who received temozolomide alone, 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 patients who received the tumor-treating fields. 

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.” ■

Stupp R, et al: JAMA 318:2306-2316, 2017. 




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