Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial.

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Version: Final published version
Serval ID
serval:BIB_9E83CBEA38DC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial.
Journal
JAMA
Author(s)
Stupp R., Taillibert S., Kanner A.A., Kesari S., Steinberg D.M., Toms S.A., Taylor L.P., Lieberman F., Silvani A., Fink K.L., Barnett G.H., Zhu J.J., Henson J.W., Engelhard H.H., Chen T.C., Tran D.D., Sroubek J., Tran N.D., Hottinger A.F., Landolfi J., Desai R., Caroli M., Kew Y., Honnorat J., Idbaih A., Kirson E.D., Weinberg U., Palti Y., Hegi M.E., Ram Z.
ISSN
1538-3598 (Electronic)
ISSN-L
0098-7484
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
314
Number
23
Pages
2535-2543
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
IMPORTANCE: Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly.
OBJECTIVE: To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma.
DESIGN, SETTING, AND PARTICIPANTS: After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis.
INTERVENTIONS: Treatment with TTFields was delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m2/d) was given for 5 days of each 28-day cycle.
MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up.
RESULTS: The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to-treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7-25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004).
CONCLUSIONS AND RELEVANCE: In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00916409.
Keywords
Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Alkylating/therapeutic use, Brain Neoplasms/mortality, Brain Neoplasms/therapy, Canada, Carmustine/therapeutic use, Chemoradiotherapy, Combined Modality Therapy/adverse effects, Combined Modality Therapy/methods, Dacarbazine/analogs & derivatives, Dacarbazine/therapeutic use, Disease Progression, Disease-Free Survival, Early Termination of Clinical Trials, Electric Stimulation Therapy/adverse effects, Electric Stimulation Therapy/methods, Europe, Female, Glioblastoma/mortality, Glioblastoma/therapy, Humans, Israel, Maintenance Chemotherapy/methods, Male, Middle Aged, Republic of Korea, United States, Young Adult
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Web of science
Create date
10/01/2016 15:26
Last modification date
20/08/2019 15:04
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