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JAMA. 2017 Dec 19;318(23):2306-2316. doi: 10.1001/jama.2017.18718.

Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial.

Author information

1
Lou and Jean MalnatiBrain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University Feinberg School of Medicine, Chicago, Illinois
2
Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
3
University Hospital Zurich and University of Zurich, Zurich, Switzerland
4
Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France
5
Tel Aviv Medical Center, Tel Aviv, Israel
6
University of California, San Diego
7
Emory University, Atlanta, Georgia
8
Tel Aviv University, Tel Aviv, Israel
9
Geisinger Health System, Danville, Pennsylvania
10
Cleveland Clinic Foundation, Cleveland, Ohio
11
Baylor University Medical Center, Houston, Texas
12
Istituto Nazionale Neurologico Carlo Besta, Milan, Italy
13
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
14
University of Texas Health Sciences Center at Houston
15
Tufts Medical Center, Boston, Massachusetts
16
Karolinska Hospital, Stockholm, Sweden
17
Washington University Barnes-Jewish Hospital, St Louis, Missouri
18
Moffitt Cancer Center, Tampa, Florida
19
University of Pennsylvania, Philadelphia
20
Novocure Ltd, Israel
21
Seoul National University Bundang Hospital, Seoul National University College of Medicine, Bundang, Korea
22
Seoul National University, Seoul, Korea
23
Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
24
Hospital Universitario de Bellvitge, Barcelona, Spain
25
Juravinski Cancer Centre, Hamilton, Ontario, Canada

Abstract

Importance:

Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor.

Objective:

To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system.

Design, Setting, and Participants:

In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis.

Interventions:

Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles).

Main Outcomes and Measures:

Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group.

Results:

Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone.

Conclusions and Relevance:

In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields 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.

Trial Registration:

clinicaltrials.gov Identifier: NCT00916409.

PMID:
29260225
PMCID:
PMC5820703
DOI:
10.1001/jama.2017.18718
[Indexed for MEDLINE]
Free PMC Article

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