Abstract
Background
Tumor Treating Fields (TTFields) are a physical anti-mitotic treatment modality characterized by their immediate mode of action and lack of a half-life. It has been shown that average monthly compliance with TTFields is correlated with overall survival in recurrent glioblastoma. Compliance ≥75% compliance (average daily use of at least 18h/d), has been suggested as a target for patients with recurrent glioblastoma receiving TTFields as monotherapy. In the EF-14 phase 3 trial in newly diagnosed glioblastoma, TTFields were applied together with temozolomide (TTFields/TMZ) and led to superior progression free (PFS) and overall survival (OS) compared to TMZ alone. We analyzed how rates of compliance with TTFields/TMZ correlated with PFS and OS in the EF-14 trial.
Material and Methods
Compliance was assessed using daily usage data from the NovoTTF-100A (Optune®) computerized log file. Compliance was calculated as percentage of 24-hour period of TTFields delivery. Patients on TTFields/TMZ were segregated into subgroups by percentage daily compliance: 0 - ≤30%; 30% - ≤50%; 50% - ≤60%; 60% - ≤70%; 70% - ≤80%; 80% - ≤90% and 90% - ≤100%. 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 in PFS and OS.
Results
A threshold value of 50% average daily compliance with TTFields was needed to extend PFS (HR 0.70 95%CI 0.47–1.05) and OS (HR 0.67 95%CI 0.45–0.99) versus TMZ alone. A trend in favor of longer PFS and OS was seen with higher compliance subgroups (>90% compliance: PFS HR 0.54 95%CI 0.37–0.79; OS HR 0.52 95%CI 0.35–0.79). At compliance >90% median survival was 24.9 months (28.7 months from diagnosis) and 5-year survival 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; for OS at compliance ≥75% vs <75%).
Conclusion
A compliance threshold of 50% with TTFields/TMZ treatment correlated with significantly improved outcomes in OS and PFS versus TMZ alone. A trend in favor of longer PFS and OS was seen at higher compliance rates (90%). Increased compliance with TTFields therapy is prognostic for improved survival in glioblastoma.