CTNI-77. EF-19, A POST-APPROVAL REGISTRY STUDY OF TUMOR TREATING FIELDS (TTFIELDS) IN RECURRENT GLIOBLASTOMA (rGBM)

Abstract

Abstract BACKGROUND Tumor Treating Fields (TTFields) are an anti-mitotic therapy of alternating electric fields delivered non-invasively to the tumor. In phase 3 studies leading to FDA-approvals, TTFields plus temozolomide (TMZ) significantly extended survival in newly diagnosed GBM, and achieved comparable survival to best standard of care (BSC) as monotherapy in recurrent GBM (rGBM). The EF-19 study evaluated efficacy of TTFields vs BSC in rGBM in post-approval real-life setting. METHODS This registry trial (192 rGBM patients, >21 yrs, KPS > 70) were treated with TTFields (200 kHz, >18h/day). Primary endpoint was overall survival (OS); secondary endpoints were OS in the per protocol (PP) population, time to treatment failure and adverse events (AEs). The registry data were compared to OS of all 117 patients in EF-11 BSC group (Stupp EJC 2012). The sample size (N=192) was based on non-inferiority log-rank test with two-sided alpha (0.05), 80% power, HR of 1.0 comparing TTFields to control with an upper one-sided 95% CI of HR < 1.375. RESULTS Median OS with TTFields versus EF-11 BSC was 7.4 versus 6.4 months, p=0.053; HR = 0.64 (95%CI 0.46–0.91, Cox-test P=0.012). Median OS (PP) with TTFields versus EF-11 BSC was 8.1 months versus 6.5 months; p=0.045; HR 0.65. OS was significantly higher TTFields as the 95% CI upper limit of HR was lower than the pre-defined threshold of 1.375. The overall incidence of AEs was lower with TTFields than EF-11 BSC (67% vs. 95%). The median time to treatment failure was longer in the TTFields arm (3.3 months (95% CI 2.6, 3.9) versus 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 common AE in the TTFields arm. CONCLUSION The results of the EF-19 registry study confirm the effectiveness and safety of TTFields monotherapy in rGBM.