title: Response assessment of NovoTTF-100A versus best physician's choice chemotherapy in recurrent glioblastoma.
abstract: The NovoTTF-100A device emits frequency-tuned alternating electric fields that interfere with tumor cell mitosis. In phase III trial for recurrent glioblastomas, NovoTTF-100A was shown to have equivalent efficacy and less toxicity when compared to Best Physician's Choice (BPC) chemotherapy. We analyzed the characteristics of responders and nonresponders in both cohorts to determine the characteristics of response and potential predictive factors. Tumor response and 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 compared between responders and nonresponders. Median response duration was 7.3 versus 5.6 months for NovoTTF-100A and BPC chemotherapy, respectively (P = 0.0009). Five of 14 NovoTTF-100A responders but none of seven BPC responders had prior low-grade histology. Mean cumulative dexamethasone dose was 35.9 mg for responders versus 485.6 mg for nonresponders in the NovoTTF-100A cohort (P < 0.0001). Hazard analysis showed delayed tumor progression in responders compared to nonresponders. Simon-Makuch-adjusted PFS was longer in responders than in nonresponders treated with NovoTTF-100A (P = 0.0007) or BPC chemotherapy (P = 0.0222). Median OS was longer for responders than nonresponders treated with NovoTTF-100A (P < 0.0001) and BPC chemotherapy (P = 0.0235). Pearson analysis showed strong correlation between response and OS in NovoTTF-100A (P = 0.0002) but not in BPC cohort (P = 0.2900). Our results indicate that the response characteristics favor NovoTTF-100A and data on prior low-grade histology and dexamethasone suggest potential genetic and epigenetic determinants of NovoTTF-100A response.
authors.affiliation: Brain Tumor Center and Neuro-Oncology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wong
authors.forename: Edwin
authors.initials: E
authors.lastname: Lok
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Swanson
authors.forename: Shiva
authors.initials: S
authors.lastname: Gautam
authors.forename: Herbert H
authors.initials: HH
authors.lastname: Engelhard
authors.forename: Frank
authors.initials: F
authors.lastname: Lieberman
authors.forename: Sophie
authors.initials: S
authors.lastname: Taillibert
authors.forename: Zvi
authors.initials: Z
authors.lastname: Ram
authors.forename: John L
authors.initials: JL
authors.lastname: Villano
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D060733:Electromagnetic Radiation; D004864:Equipment and Supplies; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008875:Middle Aged; D008938:Mitosis / Q000528:radiation effects; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*
keywords: NovoTTF-100A; recurrent glioblastoma; response