Journal article
Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial.
- Stupp R University Hospital Zurich and University of Zurich, Zurich, Switzerland2Lausanne University Hospital (CHUV), Lausanne, Switzerland.
- Taillibert S Assistance Publique des Hôpitaux de Paris, La Pitié-Salpétrière-University Hospital, Pierre and Marie Curie University, Paris, France.
- Kanner AA Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.
- Kesari S University of California, San Diego.
- Steinberg DM Tel Aviv University, Tel Aviv, Israel.
- Toms SA Geisinger Health System, Danville, Pennsylvania.
- Taylor LP Tufts Medical Center, Boston, Massachusetts.
- Lieberman F University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
- Silvani A Istituto Nazionale Neurologico Carlo Besta, Milan, Italy.
- Fink KL Baylor University Medical Center, Dallas, Texas.
- Barnett GH Cleveland Clinic Foundation, Cleveland, Ohio.
- Zhu JJ Baylor University Medical Center, Dallas, Texas13University of Texas Health Science Center, Houston.
- Henson JW Swedish Neuroscience Institute, Seattle, Washington.
- Engelhard HH University of Illinois, Chicago.
- Chen TC University of Southern California, Los Angeles.
- Tran DD Washington University Barnes-Jewish Hospital, St Louis, Missouri.
- Sroubek J Na Homolce Hospital, Prague, Czech Republic.
- Tran ND Moffitt Cancer Center, Tampa, Florida.
- Hottinger AF Lausanne University Hospital (CHUV), Lausanne, Switzerland.
- Landolfi J New Jersey Neuroscience Institute, Edison.
- Desai R Maine Medical Center, Portland.
- Caroli M Fondazione Ospedale Maggiore Policlinico, Milan, Italy.
- Kew Y Houston Methodist Hospital, Houston, Texas.
- Honnorat J Hospices Civils de Lyon, University Claude Bernard Lyon 1, Lyon, France.
- Idbaih A Assistance Publique des Hôpitaux de Paris, La Pitié-Salpétrière-University Hospital, Pierre and Marie Curie University, Paris, France.
- Kirson ED Novocure, Haifa, Israel.
- Weinberg U Novocure, Haifa, Israel.
- Palti Y Novocure, Haifa, Israel.
- Hegi ME Lausanne University Hospital (CHUV), Lausanne, Switzerland.
- Ram Z Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.
- 2015-12-17
Published in:
- JAMA. - 2015
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Alkylating
Brain Neoplasms
Canada
Carmustine
Chemoradiotherapy
Combined Modality Therapy
Dacarbazine
Disease Progression
Disease-Free Survival
Early Termination of Clinical Trials
Electric Stimulation Therapy
Europe
Female
Glioblastoma
Humans
Israel
Maintenance Chemotherapy
Male
Middle Aged
Republic of Korea
Temozolomide
United States
Young Adult
English
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.
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1001/jama.2015.16669
- PMID 26670971
- Persistent URL
- https://sonar.ch/global/documents/164688
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