Maintenance therapy with tumor-Treating fields plus temozolomide vs temozolomide alone for glioblastoma a randomized clinical trial
Roger Stupp,Roger Stupp,S. Taillibert,Andrew A. Kanner,Santosh Kesari,David M. Steinberg,Steven A. Toms,Lynne P. Taylor,Frank S. Lieberman,Antonio Silvani,Karen Fink,Gene H. Barnett,Jay-Jiguang Zhu,John W. Henson,Herbert H. Engelhard,Thomas C. Chen,David Tran,Jan Sroubek,Nam D. Tran,Andreas F. Hottinger,Joseph Landolfi,Rajiv D. Desai,Manuela Caroli,Yvonne Kew,Jérôme Honnorat,Ahmed Idbaih,Eilon D. Kirson,Uri Weinberg,Yoram Palti,Monika E. Hegi,Zvi Ram +30 more
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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.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/m 2 /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:NCT00916409read more
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Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial
Roger Stupp,Roger Stupp,Roger Stupp,Sophie Taillibert,Sophie Taillibert,Andrew A. Kanner,William L. Read,William L. Read,David M. Steinberg,Benoit Lhermitte,Steven A. Toms,Ahmed Idbaih,Manmeet Ahluwalia,Karen Fink,Francesco Di Meco,Frank S. Lieberman,Jay-Jiguang Zhu,Jay-Jiguang Zhu,Giuseppe Stragliotto,David Tran,Steven Brem,Steven Brem,Andreas F. Hottinger,Eilon D. Kirson,Gitit Lavy-Shahaf,Uri Weinberg,Chae-Yong Kim,Sun Ha Paek,Garth Nicholas,Jordi Burna,H Hirte,Michael Weller,Yoram Palti,Monika E. Hegi,Zvi Ram +34 more
TL;DR: 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 Temozolmide alone, resulted in statistically significant improvement in progression-free survival and overall survival.
Journal ArticleDOI
Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy
Christine E. Brown,Darya Alizadeh,Renate Starr,Weng L,Wagner,Araceli Naranjo,Ostberg,Melvin Blanchard,Kilpatrick J,Simpson J,Kurien A,Saul J. Priceman,Xiuli Wang,Harshbarger Tl,Massimo D'Apuzzo,Ressler Ja,Michael C. Jensen,Michael E. Barish,Chen M,Jana Portnow,Stephen J. Forman,Behnam Badie +21 more
TL;DR: Recurrent multifocal glioblastoma patients received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2) and regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid.
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A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma.
Donald M. O'Rourke,MacLean Nasrallah,Arati Desai,J. Joseph Melenhorst,Keith Mansfield,Jennifer J.D. Morrissette,Maria Martinez-Lage,Steven Brem,Eileen Maloney,Angela Shen,Randi Isaacs,Suyash Mohan,Gabriela Plesa,Simon F. Lacey,Jean-Marc Navenot,Zhaohui Zheng,Bruce L. Levine,Hideho Okada,Carl H. June,Jennifer Brogdon,Marcela V. Maus +20 more
TL;DR: The initial experience with CAR T cells in recurrent GBM suggests that although intravenous infusion results in on-target activity in the brain, overcoming the adaptive changes in the local tumor microenvironment and addressing the antigen heterogeneity may improve the efficacy of EGFRvIII-directed strategies in GBM.
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European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas
Michael Weller,Martin J. van den Bent,Jörg C. Tonn,Roger Stupp,Matthias Preusser,Elizabeth Cohen-Jonathan-Moyal,Roger Henriksson,Emilie Le Rhun,Carmen Balana,Olivier Chinot,Martin Bendszus,Jaap C. Reijneveld,F. Dhermain,Pim J. French,Christine Marosi,Colin Watts,Ingela Oberg,Geoffrey J. Pilkington,Brigitta G. Baumert,Martin J.B. Taphoorn,Monika E. Hegi,Manfred Westphal,Guido Reifenberger,Riccardo Soffietti,Wolfgang Wick,Wolfgang Wick +25 more
TL;DR: The European Association for Neuro-Oncology guideline provides recommendations for the clinical care of adult patients with astrocytic and oligodendroglial gliomas, including glioblastomas, based on the 2016 WHO classification of tumours of the central nervous system and on scientific developments since the 2014 guideline.
Journal ArticleDOI
Glioblastoma: Overview of Disease and Treatment.
TL;DR: Despite aggressive resection and combined modality adjuvant treatment, most GBMs recur and innovative treatments, such as TTFields, drugs to target molecular receptors, and immunotherapy, are promising new options.
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Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial
Roger Stupp,Monika E. Hegi,Warren P. Mason,Martin J. van den Bent,Martin J.B. Taphoorn,Robert C. Janzer,Samuel K. Ludwin,Anouk Allgeier,Barbara Fisher,Karl Belanger,Peter Hau,Alba A. Brandes,J.M.M. Gijtenbeek,Christine Marosi,Charles J. Vecht,Karima Mokhtari,Pieter Wesseling,Salvador Villà,Elizabeth Eisenhauer,Thierry Gorlia,Michael Weller,Denis Lacombe,J. Gregory Cairncross,René-Olivier Mirimanoff +23 more
TL;DR: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up, and a benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years.
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