Meta-analysis: TTFields added to SoC improves OS in newly diagnosed GBM in real-world setting

Results of a systematic review and meta-analysis suggest that adding tumour-treating fields (TTFields) to standard chemoradiotherapy (CRT) significantly prolongs overall survival (OS) for patients with newly diagnosed glioblastoma multiforme (GBM) treated in the real-world setting.

TTFields are alternating electric fields that exert physical forces on cancer cells, and work by disrupting processes critical to cancer cell viability and progression. [Clin Cancer Res 2018;24:266-275; Cancer Res 2004;64:3288-3295; Cancers 2020;12:3016] TTFields are delivered noninvasively and locoregionally to the tumour through arrays placed on the skin, which are powered through a portable battery device. [JAMA 2017;318:2306-2316]

“Increasing number of global approvals and collective experience with TTFields in recent years have given way to multiple institution-led studies and case reports of TTFields use among patients with newly diagnosed GBM, reflecting clinical uptake and potential utility. However, a clear understanding of TTFields’ performance [in the real world] is [still] lacking, and perception of clinical benefit continues to vary across treatment centres,” wrote the researchers. “Utilizing a systematic review and meta-analytic framework, we sought to assess whether the addition of TTFields to standard of care [SoC] is associated with prolonged survival for patients with newly diagnosed GBM, and whether greater usage of the device translates to benefit in clinical practice.”

The researchers identified seven studies (n=1,430) comparing TTFields plus SoC CRT vs SoC alone, which they included in a pooled analysis of OS. Five of the seven studies (n=1,214) used hazard ratios (HRs) for evaluating the impact of device usage rate on patient survival and were included in OS by usage analysis. Survival was evaluated across the 75 percent device usage rate threshold (average of 18 hours per day), which most centres have established as the recommended minimum level for optimal benefit. [J Neurooncol 2023;164:1-9]

Meta-analysis results revealed significantly improved OS with TTFields plus SoC vs SoC alone in patients with newly diagnosed GBM (HR, 0.63; 95 percent confidence interval [CI], 0.53–0.75; p<0.001). “Heterogeneity among studies was low, and a sensitivity analysis indicated that the pooled effect was robust and not dependent on any individual study,” remarked the researchers.

A subgroup analysis was conducted to specifically assess the impact of TTFields on OS in the real-world setting. Among post-approval studies, the pooled median OS was 22.6 months for TTFields-treated patients and 17.4 months for patients not receiving TTFields. The 2- and 4-year OS rates were 46.8 percent and 32.3 percent, and 22.7 percent and 8.0 percent for the TTFields and non-TTFields groups, respectively. “Meta-analysis of post-approval studies was consistent with the full dataset in showing a survival benefit with TTFields added to standard CRT [HR, 0.66; 95 percent CI, 0.54–0.82; p<0.001],” reported the researchers.

Usage meta-analysis indicated an improvement in OS when average device use was ≥75 percent vs <75 percent (HR, 0.60; 95 percent CI, 0.48–0.73; p<0.001). In a subgroup analysis of patients treated exclusively in the real world, the survival benefit was maintained with higher device usage (HR, 0.56; 95 percent CI, 0.41–0.76; p<0.001).

“Our meta-analysis suggests that the addition of TTFields to standard CRT significantly prolongs OS for patients with newly diagnosed GBM treated in the real-world setting. While device usage rate varies in clinical practice, the association between high device usage rate and survival is consistent with results in patients treated in pivotal clinical trials, with many patients able to attain high usage in the real world,” concluded the researchers.