NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality1 Background2 Methods2.1 Patient selection2.2 Study design and treatment2.3 Patient surveillance and follow up2.4 Statistical analysis2.5 Organisational aspects2.6 Role of the funding source3 Results3.1 Patients3.2 Patient disposition, treatment and compliance3.3 Survival, progression and radiological response3.4 Safety and toxicity3.5 Quality of life3.6 Treatment after progression4 DiscussionConflict of interest statementAcknowledgementsAppendix A Supplementary dataAppendix A Supplementary dataReferencesNovoTTF-100A versus physician’s choice chemotherapyin recurrent glioblastoma: A randomised phase III trialof a novel treatment modalityRoger Stuppa,⇑, Eric T. Wongb, Andrew A. Kannerc, David Steinbergd,Herbert Engelharde, Volkmar Heideckef, Eilon D. Kirsong, Sophie Tailliberth,Frank Liebermanni, Vladimir Dbaly´j, Zvi Ramc, J. Lee Villanoe, Nikolai Rainovf,Uri Weinbergg, David Schiffk, Lara Kunschnerl, Jeffrey Raizerm, Jerome Honnoratn,Andrew Sloano, Mark Malkinp, Joseph C. Landolfiq, Franz Payerr,Maximilian Mehdorns, Robert J. Weilt, Susan C. Pannullou, Manfred Westphalv,Martin Smrckaw, Lawrence Chinx, Herwig Kostrony, Silvia Hoferz, Jeffrey Bruceaa,Rees Cosgroveab, Nina Paleologousac, Yoram Paltig, Philip H. GutinadaCentre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, SwitzerlandbHarvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, United StatescTel Aviv Medical Center, Tel Aviv, IsraeldDepartment of Biostatistics, Tel Aviv University, Tel Aviv, IsraeleUniversity of Illinois at Chicago, Chicago, IL, United StatesfAugsburg Clinic, Augsburg, GermanygNovocure Ltd., Haifa, IsraelhHospital de la Pitie-Salpetriere, Paris, FranceiUniversity of Pittsburgh Medical Center, Pittsburgh, PA, United StatesjNa Homolce Hospital, Prague, Czech RepublickUniversity of Virginia, Charlottesville, VA, United StateslAllegheny Neurological Brain Tumor Center, Pittsburgh, PA, United StatesmNorthwestern University, Chicago, IL, United StatesnDepartment of Neuro-Oncology, Hospices Civils de Lyon, Universite´Claude Bernard, Lyon, FranceoUniversity Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH, United StatespMedical College of Wisconsin, Milwaukee, WI, United StatesqNew Jersey Neuroscience Institute at JFK Medical Center, Edison, NY, United StatesrUniversity Graz, Graz, AustriasUniversity of Kiel, Kiel, GermanytThe Cleveland Clinic Foundation-Taussig Cancer Center, Cleveland, OH, United StatesuNew York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY, United StatesvUniversity of Hamburg, Hamburg, GermanywBrno University Hospital, Brno, Czech RepublicxBoston Medical Center, Boston, MA, United States0959-8049/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.ejca.2012.04.011⇑Corresponding author: Address: Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois (CHUV), 46, rue du Bugnon, Lausanne1011, Switzerland. Tel.: +41 21 314 0156; fax: +41 21 314 0737.E-mail address: [email protected] (R. Stupp).European Journal of Cancer (2012) 48, 2192– 2202Available at www.sciencedirect.comjournal homepage: www.ejconline.comyUniversity of Innsbruck, AustriazUniversity Hospital Zurich, SwitzerlandaaColumbia University Medical Center, New York, NY, United StatesabLahey Clinic, Boston, MA, United StatesacNorthShore University Health System, Evanston, IL, United StatesadMemorial Sloan Kettering Cancer Center, New York, NY, United StatesAvailable online 18 May 2012KEYWORDSGlioblastomaBrain tumourChemotherapyRandomised trialAbstract Purpose: NovoTTF-100A is a portable device delivering low-intensity, intermedi-ate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields(TTF), a completely new therapeutic modality in cancer treatment, physically interfere withcell division.Methods: Phase III trial of chemotherapy-free treatment of NovoTTF (20–24 h/day) versusactive chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival.Results: Patients (median age 54 years (range 23–80), Karnofsky performance status 80%(range 50–100) were randomised to TTF alone (n = 120) or active chemotherapy control(n = 117). Number of prior treatments was two (range 1–6). Median survival was 6.6 versus6.0 months (hazard ratio 0.86 [95% CI 0.66–1.12]; p = 0.27), 1-year survival rate was 20%and 20%, progression-free survival rate at 6 months was 21.4% and 15.1% (p = 0.13), respec-tively in TTF and active control patients. Responses were more common in the TTF arm (14%versus 9.6%, p = 0.19). The TTF-related adverse events were mild (14%) to moderate (2%)skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16%(p = 0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life anal-yses favoured TTF therapy in most domains.Conclusions: This is the first controlled trial evaluating an entirely novel cancer treatmentmodality delivering electric fields rather than chemotherapy. No improvement in overall sur-vival was demonstrated, however efficacy and activity with this chemotherapy-free treatmentdevice appears comparable to chemotherapy regimens that are commonly used for recurrentglioblastoma. Toxicity and quality of life clearly favoured TTF.Ó 2012 Elsevier Ltd. All rights reserved.1. BackgroundGlioblastoma is the most prevalent primary mali g-nant brain tumour in adults. Median survival with opti-mal therapy is only 15 months from diagnosis, and mosttumours recur within 9 months of initial treatment.1Atthe time of disease recurrence, treatment options forglioblastoma patients are limited. Repeat surgery maybe considered in approximately 20% of patients,2–4andre-irradiation is possible in rare circumstances. For mostpatients chemotherapy is indicated at disease recurrence,with the choice of drug varying greatly. In the UnitedStates, bevacizumab has been provisionally approvedfor recurrent glioblastoma, while the European Medi-cines Agency (EMEA) rejected the application in theabsence of a controlled trial.5,6Cytotoxic agents mostfrequently used are alkylating agents like nitrosoureas(e.g. lomustine [CCNU] or carmustine [BCNU],7pro-carbazine8or re-treatment with
View Full Document
Unlocking...