Background: Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable medical device. In phase 3 studies leading to FDA approvals, TTFields significantly extended survival in newly diagnosed GBM when added to maintenance temozolomide, and achieved comparable survival outcome to best standard of care (BSC) when used as monotherapy in recurrent GBM. The aim of the EF-19 study was to confirm the efficacy of TTFields versus BSC for recurrent GBM in the post-approval real-life setting.
Method: This non-inferiority, prospective, non-randomized, post approval registry trial enrolled 192 recurrent GBM patients (>21 years, KPS > 70). All patients were treated with TTFields (200 kHz, >18h/day). Eligibility criteria included histological diagnosis of GBM, past treatment with the Stupp protocol for the primary disease and radiological evidence of progression in the supratentorial region. The primary endpoint was overall survival (OS); secondary endpoints included OS in the per protocol (PP) population (>1 course of TTFields or BSC in each respective arm), time to treatment failure and incidence of adverse events. The TTFields patient registry data were compared to OS of all 117 recurrent GBM patients in the BSC group of the EF-11 pivotal trial (Stupp R., et al., EJC 2012). The sample size of 192 patients (10% loss to follow up) was determined based on non-inferiority log-rank test with a two-sided alpha level of 0.05 and a power of 80%, comparing time to event (i.e., death) between patients treated with TTFields and BSC. The analysis was based on true hazard ratio (HR) of 1.0 comparing TTFields to control with an upper one-sided 95% confidence bound of HR is not exceeding 1.375. Result: Median OS in patients treated with TTFields versus EF-11 BSC was 7.4 vs. 6.4 months, p=0.053; HR = 0.64 (95%CI 0.46-0.91, Cox-test P=0.012). In the PP population, the median OS with TTFields versus EF-11 BSC was 8.1 months vs. 6.5 months, respectively; p=0.045; HR 0.65. The results show a significant superiority HR of overall survival between the ITT groups, as superiority 95% confident interval upper limit of the HR was lower than the pre-defined threshold for non-inferiority for interval bound of 1.375. The overall incidence of adverse event was lower in the TTFields arm (67% vs. 95%) vs. EF-11 BSC arm. The median time to treatment failure was longer in the TTFields arm (3.3 months (95% CI 2.6, 3.9)) compared to the BSC arm (1.6 months; 95% CI 1.1, 1.9); HR=0.53 (95% CI 0.41, 0.68, p<0.0001). Skin AE was the most frequently reported AEs in TTFields-treated patients; No unexpected adverse events were reported with TTFields. Conclusion: The EF-19 confirmed the effectiveness and safety of TTFields as monotherapy in recurrent GBM.
Citation Format: Jay-Jiguang Zhu, Robert T. O'Donnell, Zvi Ram. EF-19 - A post-approval registry study of TTFields for the treatment of recurrent glioblastoma (GBM) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT211.