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

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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,<jats:italic>MGMT</jats:italic>methylation status, age, region, and performance status was used to investigate the effect of compliance on PFS and OS.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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,<jats:italic>MGMT</jats:italic>methylation status, age, region and performance status (HR 0.78; p = 0.031; OS at compliance ≥ 75% vs. < 75%).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>