Response assessment of NovoTTF-100A versus bestphysician’s choice chemothera py in rec urrent glioblastoma

ORIGINAL RESEARCHResponse assessment of NovoTTF-100A versus bestphysician’s choice chemothera py in rec urrent glioblastomaEric T. Wong1, Edwin Lok1, Kenneth D. Swanson1, Shiva Gautam2, Herbert H. Engelhard3,Frank Lieberman4, Sophie Taillibert5, Zvi Ram6& John L. Villano71Brain Tumor Center and Neuro-Oncology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts2Division of Biostatistics, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts3Departments of Neurological Surgery and Bioengineering, University of Illinois Hospital and Health Sciences System, Chicago, Illinois4Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania5Fe´de´ration de Neurologie 2, Groupe Hospitalier Pitie´-Salpe´triere, Universite´Pierre et Marie Curie Paris VI, Paris, France6Department of Neurosurgery, Tel Aviv Medical Center, Tel Aviv, Israel7Markey Cancer Center, University of Kentucky Health Care, Lexington, KentuckyKeywordsNovoTTF-100A, recurrent glioblastoma,responseCorrespondenceEric T. Wong, Brain Tumor Center andNeuro-Oncology Unit, Department ofNeurology, Beth Israel Deaconess MedicalCenter, 330 Brookline Avenue,Boston, MA 02215.Tel: 617-667-1665; Fax: 617-667-1664;E-mail: ewong@bidmc.harvard.eduFunding InformationThis work was supported in part by A ReasonTo Ride research fund.Received: 7 December 2013; Revised: 16January 2014; Accepted: 17 January 2014Cancer Medicine 2014; 3(3): 592–602doi: 10.1002/cam4.210AbstractThe NovoTTF-100A device emits frequency-tuned alternating electric fields thatinterfere with tumor cell mitosis. In phase III trial for recurrent glioblastomas,NovoTTF-100A was shown to have equivalent efficacy and less toxicity whencompared to Best Physician’s Choice (BPC) chemotherapy. We analyzed thecharacteristics of responders and nonresponders in both cohorts to determinethe characteristics of response and potential predictive factors. Tumor responseand progression were determined by Macdonald criteria. Time to response,response duration, progression-free survival (PFS)  Simon–Makuch correction,overall survival (OS), prognostic factors, and relative hazard rates were comparedbetween responders and nonresponders. Median response duration was 7.3versus 5.6 months for NovoTTF-100A and BPC chemotherapy, respectively(P = 0.0009). Five of 14 NovoTTF-100A responders but none of seven BPCresponders had prior low-grade histology. Mean cumulative dexamethasone dosewas 35.9 mg for responders versus 485.6 mg for nonresponders in theNovoTTF-100A cohort (P < 0.0001). Hazard analysis showed delayed tumorprogression in responders compared to nonresponders. Simon–Makuch-adjustedPFS was longer in responders than in nonresponders treated with NovoTTF-100A (P = 0.0007) or BPC chemotherapy (P = 0.0222). Median OS was longerfor responders than nonresponders treated with NovoTTF-100A (P < 0.0001)and BPC chemotherapy (P = 0.0235). Pearson analysis showed strong correlationbetween response and OS in NovoTTF-100A (P = 0.0002) but not in BPC cohort(P = 0.2900). Our results indicate that the response characteristics favorNovoTTF-100A and data on prior low-grade histology and dexamethasone sug-gest potential genetic and epigenetic determinants of NovoTTF-100A response.