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. 2019 Jan;141(2):467-473.
doi: 10.1007/s11060-018-03057-z. Epub 2018 Dec 1.

Increased compliance with tumor treating fields therapy is prognostic for improved survival in the treatment of glioblastoma: a subgroup analysis of the EF-14 phase III trial

S A Toms  1 , C Y Kim  2 , G Nicholas  3 , Z Ram  4
Affiliations

Increased compliance with tumor treating fields therapy is prognostic for improved survival in the treatment of glioblastoma: a subgroup analysis of the EF-14 phase III trial

S A Toms et al. J Neurooncol. 2019 Jan.

Abstract

Background: Tumor treating fields (TTFields) is a non-invasive, antimitotic therapy. In the EF-14 phase 3 trial in newly diagnosed glioblastoma, TTFields plus temozolomide (TTFields/TMZ) improved progression free (PFS) and overall survival (OS) versus TMZ alone. Previous data indicate a ≥ 75% daily compliance improves outcomes. We analyzed compliance data from TTFields/TMZ patients in the EF-14 study to correlate TTFields compliance with PFS and OS and identify potential lower boundary for compliance with improved clinical outcomes.

Methods: Compliance was assessed by usage data from the NovoTTF-100A device and calculated as percentage per month of TTFields delivery. TTFields/TMZ patients were segregated into subgroups by percent monthly compliance. A Cox proportional hazard model controlled for sex, extent of resection, MGMT methylation status, age, region, and performance status was used to investigate the effect of compliance on PFS and OS.

Results: A threshold value of 50% compliance with TTFields/TMZ improved PFS (HR 0.70, 95% CI 0.47-1.05) and OS (HR 0.67, 95% CI 0.45-0.99) versus TMZ alone with improved outcome as compliance increased. At compliance > 90%, median survival was 24.9 months (28.7 months from diagnosis) and 5-year survival rate was 29.3%. Compliance was independent of gender, extent of resection, MGMT methylation status, age, region and performance status (HR 0.78; p = 0.031; OS at compliance ≥ 75% vs. < 75%).

Conclusion: A compliance threshold of 50% with TTFields/TMZ correlated with significantly improved OS and PFS versus TMZ alone. Patients with compliance > 90% showed extended median and 5-year survival rates. Increased compliance with TTFields therapy is independently prognostic for improved survival in glioblastoma.

Trial registration: ClinicalTrials.gov NCT00916409.

Keywords: Compliance; Glioblastoma; Monthly usage; Tumor treating fields.

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Conflict of interest statement

S. A. Toms, C. Y. Kim and G. Nicholas have nothing to disclose. Z. Ram reports a research grant (principal investigator and consultant) with Novocure, Ltd. and ownership interest (stock) in Novocure, Ltd.

Figures

Fig. 1
Fig. 1
Forest plots show the effect of treatment compliance with TTFields plus TMZ on PFS and OS. A threshold value of 50% compliance with TTFields plus TMZ was needed to show a significant extension of OS compared to TMZ alone. Both PFS and OS were extended with treatment compliance levels > 50%. A trend in favor of longer PFS and OS was seen with higher rates of treatment compliance
Fig. 2
Fig. 2
Newly diagnosed GBM patients had maximal treatment benefit from TTFields plus TMZ with compliance rates > 90% with a median overall survival of 24.9 months (28.7 months from diagnosis)
Fig. 3
Fig. 3
The annual survival rate was highest for newly diagnosed GBM patients with compliance rates > 90% with a 29.3% survival rate over 5 years from randomization
See this image and copyright information in PMC

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