Purpose/Objective(s): Tumor Treating Fields (TTFields) are an antineoplastic treatment delivering low-intensity (1-3 V/cm), intermediatefrequency (100-500 kHz), alternating electric fields through 2 pairs of skin-affixed, locoregionally applied transducer arrays to target tumor bed. TTFields are FDA-approved for glioblastoma (GBM; 200 kHz optimal frequency) and unresectable malignant pleural mesothelioma (150 kHz). Safety and effectiveness were demonstrated in the Phase 3 EF-11 and EF-14 clinical trials in recurrent GBM (rGBM) and in newly diagnosed GBM (ndGBM), respectively. The main TTFields-related adverse event (AE) was array-associated manageable skin irritation. We report AEs from TTFields-treated patients in the real-world, clinical practice setting. Materials/Methods: Unsolicited, global, post-market surveillance data from TTFields-treated patients (October 2011eFebruary 2019) were retrospectively analyzed using MedDRA v21.1 preferred terms, stratified by region (US, EMEA [Europe, Middle East, Africa], or Japan), diagnosis (ndGBM, rGBM, anaplastic astrocytoma and anaplastic oligodendroglioma, or other brain tumors that includes brain metastases from different cancer types), and years of age (<18, pediatric; 18 to 64, adults; or 65, elderly). Results: Of 11,029 patients, 53% had ndGBM, 39% had rGBM (at any line of recurrence), 6% had anaplastic astrocytoma and anaplastic oligodendroglioma, and 1% had other brain tumors. Most were adults (73%) and 26% were elderly (65 years of age). The majority of patients were males (n Z 7313; 66.3%) compared to females (n Z 3716; 33.7%), with a ratio representative of a typical GBM population. The most reported TTFields-related AE was array-associated local skin reaction, with an incidence of 38% in ndGBM, 29% in rGBM, 38% in anaplastic astrocytoma and anaplastic oligodendroglioma, and 31% in other brain tumors; as well as 37% in pediatric, 34% in adult, and 36% in elderly patients. Most skin AEs were mild to moderate and resolved with no treatment or over the counter topical ointments. Incidence of other TTFields-related AEs in patients with ndGBM and rGBM, respectively, included heat sensation (under-array warmth; 11%, 10%), electric sensation (under-array tingling; 11%, 9%), and headache (7%, 6%). Conclusion: This post-marketing, retrospective, global, TTFields safety surveillance analysis revealed no new safety signals, with favorable safety and tolerability comparable to published TTFields/GBM trials. The most common TTFields-related AE was array-associated local skin reaction on the scalp. The safety profile of TTFields remained consistent among subgroups (diagnosis, age, or region) and total cohort, indicating feasibility in multiple subpopulations, including elderly patients.
