Tumor Treating Fields (TTFields) for Newly Diagnosed Glioblastoma in the Real World: A Systematic Review and Survival Meta-Analysis

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Tumor Treating Fields (TTFields) are electric fields that exert forces on cancer cells, disrupting processes critical for cancer cell viability and tumor progression. TTFields therapy is FDA-approved for patients with newly diagnosed glioblastoma (GBM) on the basis of the randomized controlled EF-14 study (NCT00916409). Subsequent approvals and increased worldwide adoption of TTFields has led to the question of whether or not a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role. PubMed, Embase, and the Cochrane Library were searched using pre-defined terms, to identify clinical studies (including comparative and single-cohort studies) evaluating overall survival (OS) in adult patients with GBM treated with TTFields therapy added to radiochemotherapy. The Cochran Q test was used to assess inter-study heterogeneity, and results were quantified using the Higgins I2 statistic. Data were pooled, and a survival curve created using a distribution-free random-effects method. Records identified from the literature search were screened and distilled using pre-specified methods, down to 8 studies evaluating the clinical efficacy of TTFields therapy in newly diagnosed GBM (spanning diverse geographic regions). Six studies (reporting on a total of 1378 patients) compared the addition of TTFields therapy to standard of care (SOC) vs SOC alone, and were included in a pooled analysis for OS. Meta-analysis of data from the 6 studies indicated a significant OS benefit for patients receiving TTFields therapy vs those who did not (hazard ratio [HR]: 0.62; 95% CI, 0.52-0.73; P < 0.001). Sensitivity analysis confirmed the pooled effect was robust and not dependent on any individual study. Of the 6 included in the analysis, 5 were post-approval for which the pooled median OS was 22.2 months (95% CI, 17.3-42.6) vs 17.3 months (95% CI, 13.6-22.0) for the TTFields/SOC group and the SOC group, respectively. Rates of gross total resection were numerically higher in the real-world setting, irrespective of TTFields use. Among studies reporting data on TTFields device usage, an average device usage rate of 75% or higher was found to consistently correlate with prolonged OS when compared to an average usage rate < 75% (pooled HR: 0.63; 95% CI, 0.48-0.83; P = 0.001). Meta-analysis of comparative studies suggests a significant OS benefit when TTFields therapy is added to standard radiochemotherapy for patients with newly diagnosed GBM, and that a ≥ 75% usage rate may translate to clinical benefit in the real-world setting.