Abstract
PURPOSE: Tumor Treating Fields (TTFields) therapy, a noninvasive, anti-mitotic treatment modality, is approved for recurrent glioblastoma (rGBM) and newly diagnosed GBM based on phase III, EF-11 (NCT00379470) and EF-14 (NCT00916409) studies, respectively. The EF-19 study aimed to evaluate efficacy and safety of TTFields monotherapy (200 kHz) vs physicians' choice standard of care (PC-SOC; EF-11 historical control group) in rGBM. METHODS: A prospective, post-marketing registry study of adults with supratentorial rGBM treated with TTFields therapy was conducted. Primary endpoint was overall survival (OS; intent-to-treat [ITT] population) and secondary endpoint was OS per-protocol (PP). Subgroup and toxicity analyses were conducted. RESULTS: Median OS (ITT population) was comparable with TTFields monotherapy vs PC-SOC (7.4 vs 6.4 months, log-rank test P = 0.053; Cox test hazard ratio [HR] [95% CI], 0.66 [0.47-0.92], P = 0.016). The upper-bound HR (95% CI) was lower than pre-defined noninferiority (1.375 threshold). In the PP population, median OS was significantly longer for TTFields monotherapy vs PC-SOC (8.1 vs 6.4 months; log-rank test P = 0.017; Cox test HR [95% CI], 0.60 [0.42-0.85], P = 0.004). TTFields therapy showed increased benefit with extended use (≥ 18 h/day [averaged over 28 days]). TTFields therapy-related adverse events (AEs) by body system were lower vs PC-SOC: mainly mild-to-moderate skin AEs. CONCLUSION: In the real-world setting, TTFields monotherapy showed comparable (ITT population) and superior (PP population) OS vs PC-SOC in rGBM. In line with previous results, TTFields therapy showed a favorable safety profile vs chemotherapy, without new safety signals/systemic effects. TRIAL REGISTRATION: NCT01756729, registered December 20, 2012.