Phase 3 EF-14 trial of tumor treating fields plus temozolomide (TTFields/TMZ) versus TMZ alone in newly diagnosed glioblastoma: Application of RTOG-RPA scores on study population

Background: In the simplified recursive partitioning analysis (RPA) model for survival of glioblastoma patients by the Radiation Therapy Oncology Group (RTOG) patients are divided into three prognostic groups based on four variables: age, performance status, extent of resection, and neurologic function. The EF-14 phase 3 trial of TTFields/TMZ compared to TMZ alone showed that adding TTFields to TMZ increased overall survival (OS) of newly diagnosed glioblastoma patients. RTOG-RPA scores were applied on the phase 3 EF-14 patient data.

Methods: We applied the RTOG-RPA scores on the EF-14 population. OS of both arms of the EF-14 trial were compared to the original validation cohort used to develop the simplified RTOG-RPA model.

Results: OS for the TMZ alone arm were comparable to the RTOG validation dataset in all three RPA classes. OS in the TTFields/TMZ arm were improved compared to both the TMZ alone arm and the RTOG validation cohort in all three RPA classes. The 3-year OS for the RTOG, EF-14 TMZ alone and EF-14 TMZ/TTFields cohorts were: RPA Class III – 20%, 25% and 39%; RPA Class IV: 7%, 15% and 23%; RPA Class V+VI: 1%, 9% and 20%, respectively. Median OS was significantly longer in the TTFields/TMZ arm than the TMZ alone arm for RPA Class III (26.2 versus 20.0 months, p=0.030) and RPA Class IV (20.0 versus 15.6 months, p=0.0005) but not for RPA Class V+VI (10.9 versus 12.6 months, p=0.213).

Conclusions: When applying the simplified RTOG-RPA model, TTFields/TMZ compared to TMZ alone showed improved OS out to 3 years, regardless of patients’ prognostic factors. This analysis validates the consistency of the EF-14 trial results with historical control data.