Clinical Efficacy of Tumor Treating Fields for Recurrent Glioblastoma

Abstract

Recurrent glioblastoma is defined by growth of the enhancing areas on MRI according to the Macdonald’s or Response Assessment in Neuro-Oncology (RANO) criteria but the extent of the tumor is much larger than that can be seen on neuroimaging. Patient prognosis is poor and survival is short. The Optune device is an FDA-approved treatment for recurrent glioblastoma and it uses Tumor Treating Fields (TTFields) to disrupt tumor cells as they undergo mitosis. In the pivotal EF-11 phase III trial that compared TTFields with Best Physician’s Choice chemotherapy, the two treatments had comparable efficacy with a respective median overall survival of 6.6 and 6.0 months and a hazard ratio of 0.86 (p = 0.27). The median progression free survival of TTFields and chemotherapy was 2.2 months and 2.1 months, respectively, with a hazard ratio of 0.81 (p = 0.16). The most common adverse events associated with the device were grade 1 or 2 scalp dermatitis, and shifting of the arrays slightly during array change and applying topical corticosteroid can minimize this irritation. There were far less hematological and gastrointestinal toxicities when compared to chemotherapy. In post hoc analyses of EF-11, secondary glioblastomas and low dexamethasone usage were notable prognostic factors for survival. In the TTField monotherapy cohort, the median overall survival was 11.0 months among subjects who used ≤4.1 mg/day dexamethasone and 4.8 months among those who took >4.1 mg/day (χ ² = 34.6, p < 0.0001). This dexamethasone effect was also found in the chemotherapy cohort but in a less robust fashion, with subjects who used ≤4.1 mg/day of dexamethasone having a median overall survival of 8.9 months as compared to those who used >4.1 mg/day having a median overall survival of 6.0 months (χ ² = 10.0, p = 0.0015). Other prognostic factors include a compliance rate of ≥80 %, no prior treatment with bevacizumab, and Karnofsky performance status ≥80. Therefore, multiple intrinsic and extrinsic factors can modulate the outcome of the recurrent glioblastoma under the influence of TTFields.