Post hoc analyses of intention-to-treat population in phase III comparison of NovoTTF-100A™ system versus best physician's choice chemotherapy

Abstract

We performed a treatment-based analysis of data from the pivotal phase III trial of the NovoTTF-100A System™ versus best physician's choice (BPC) chemotherapy in patients with recurrent glioblastoma multiforme (GBM), with particular focus on efficacy in patients using NovoTTF Therapy as intended. Median overall survival (OS) was compared for recurrent GBM patients receiving at least one full cycle of treatment with NovoTTF-100A System or BPC chemotherapy (modified intention-to-treat [mITT] population) in the recently reported phase III trial. The relationship between NovoTTF-100A System compliance and OS was evaluated in the ITT population. Kaplan-Meier analyses examined treatment-related differences in OS for various patient subgroups. Median OS was significantly higher in patients receiving ≥1 course of NovoTTF Therapy versus BPC (7.7 v 5.9 months; hazard ratio, 0.69; 95% confidence interval [CI], 0.52-0.91; P =.0093). Median OS was also significantly higher in patients receiving NovoTTF Therapy with a maximal monthly compliance rate ≥75% ( ≥18 hours daily) versus those with a<75% compliance rate (7.7 v 4.5 months; P =.042), and Kaplan-Meier analysis demonstrated a significant trend for improved median OS with higher compliance (P =.039). Additional post hoc analysis showed significantly higher median OS with NovoTTF Therapy than with BPC for patients with prior low-grade glioma, tumor size ≥18 cm2, Karnofsky performance status ≥80, and those who had previously failed bevacizumab therapy. When used as intended in mITT patients with recurrent GBM, NovoTTF Therapy provides an OS benefit compared with chemotherapy in patients with recurrent GBM. This contrasts with the equivalent efficacy reported previously based on analysis of all randomized ITT subjects, including many who did not receive a full cycle of treatment. Higher NovoTTF Therapy compliance corresponds with greater survival benefit in the present study.