Abstract

INTRODUCTION：Tumor Treating Fields （TTFields; antimitotic treatment） delivers low-intensity, intermediate-frequency, alternating electric fields through skin-applied transducer arrays. TTFields （200 kHz） was FDA-approved in glioblastoma （GBM）, based on the phase 3 EF-11 （recurrent GBM, rGBM） and EF-14 （newly diagnosed GBM, ndGBM） trials. The most common TTFields-related adverse event （AE） in both trials was array-associated skin irritation. We now report on TTFields-related AEs in the real-world, clinical practice setting.

METHODS：Unsolicited, post-marketing surveillance data from TTFields-treated patients （October 2011-February 2019） were retrospectively analyzed using MedDRA v21.1 preferred terms, stratified by region （US, EMEA [Europe, Middle East, Africa], Japan）, diagnosis （ndGBM, rGBM, anaplastic astrocytoma/oligodendroglioma, other brain tumors）, and age （< 18 [pediatric], 18-64 [adults], ≥ 65 [elderly]; years of age）.

RESULTS：Of 11,029 patients, 53% were diagnosed with ndGBM and 39% were diagnosed with rGBM at any line of disease recurrence. Most were adults （73%）, 26% were elderly, and the male-to-female ratio was ~ 2:1 （close to published ratios of typical GBM populations）. The most commonly reported TTFields-related AE was array-associated skin reaction, occurring in patients with ndGBM （38%）, rGBM （29%）, anaplastic astrocytoma/oligodendroglioma （38%）, and other brain tumors （31%）; as well as 37% of pediatric, 34% of adult, and 36% of elderly patients. Most skin AEs were mild/moderate and manageable. Other TTFields-related AEs in patients with ndGBM/rGBM included under-array heat sensation （warmth; 11%, 10%, respectively） and electric sensation （tingling; 11%, 9%, respectively）, and headache （7%, 6%, respectively）.

CONCLUSIONS：This TTFields safety surveillance analysis in > 11,000 patients revealed no new safety concerns, with a favorable safety profile comparable with published TTFields/GBM trials. The safety profile remained consistent among subgroups, suggesting feasibility in multiple populations, including elderly patients.

KEYWORDS：Glioblastoma; Real-world; Safety surveillance; Skin adverse events; TTFields; Tolerability.