Prospective Randomized Trial of TTFields with Chemoradiation in Newly Diagnosed Glioblastoma

Abstract Background Tumor-Treating Fields (TTFields) have demonstrated efficacy in newly diagnosed glioblastoma (ndGBM) when combined with adjuvant temozolomide (TMZ). Preclinical studies suggest that TTFields enhance the therapeutic effect of radiotherapy (RT), providing a rationale for concurrent administration with RT. This phase 2 randomized trial evaluated the addition of TTFields to standard RT and TMZ, followed by adjuvant TMZ with TTFields, in patients with ndGBM. Methods Patients were randomized prior to chemoradiation to receive RT and TMZ with or without concurrent TTFields, followed by maintenance TMZ with TTFields in both groups. The evaluable cohort, defined as an exploratory analysis, included patients who completed at least 4-weeks of RT (≥40Gy) and TTFields in the experimental arm The primary endpoint, based on the intention-to-treat(ITT) population, was 1-year progression-free survival(PFS12). Secondary endpoints included PFS, overall-survival(OS) and safety. Results Sixty-six patients were randomized (experimental n = 32;control n = 34). In the intention-to-treat population, PFS12 favored the experimental group (28.7% vs.17.3%) but did not reach statistical significance(p = 0.146). Median PFS was 5.4vs.4.13 months (p = 0.14) and median OS was 18.5 vs16.5 months(p = 0.95) respectively. In the evaluable cohort (n = 54), PFS12 favored experimental group (37.5% vs.17.3%,p=0.06), with a significantly longer median PFS (9.9 vs.4.1 months, p = 0.016). Median OS favored the experimental group (25.9 vs.16.6months, p = 0.308). Treatment was well tolerated, with adverse events similar between groups. Conclusions Early integration of TTFields with chemoradiation in ndGBM is safe, feasible. Although the primary endpoint was not met, observed survival trends support further evaluation in larger multicenter trials to confirm the potential benefit of concurrent TTFields with chemoradiation.