AUTHOR=Ram Zvi , Kim Chae-Yong , Hottinger Andreas F. , Idbaih Ahmed , Nicholas Garth , Zhu Jay-Jiguang 

TITLE=Efficacy and Safety of Tumor Treating Fields (TTFields) in Elderly Patients with Newly Diagnosed Glioblastoma: Subgroup Analysis of the Phase 3 EF-14 Clinical Trial

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.671972

DOI=10.3389/fonc.2021.671972

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Understudied elderly patients comprise a large segment of high-risk patients with glioblastoma (GBM) that are challenging to treat. Tumor Treating Fields (TTFields) is a locoregional, noninvasive, antimitotic therapy delivering low-intensity, intermediate-frequency alternating electric fields to the tumor. In the phase 3 EF-14 clinical trial, TTFields (200 kHz) improved median progression-free survival (PFS) and median overall survival (OS) in patients with newly diagnosed GBM (ndGBM) when added concomitantly to maintenance temozolomide (TMZ). This EF-14 subgroup analysis evaluated the safety and efficacy of TTFields in elderly patients.</p></sec><sec><title>Methods</title><p>All 134 patients who are ≥65 years of age were included (TTFields/TMZ combination, n=89; TMZ monotherapy, n=45; 2:1 ratio of randomization). PFS and OS were analyzed using Kaplan–Meier methodology (α=0.05). Health-related quality-of-life (HRQoL) was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire QLQ-C30 supplemented with the brain tumor module (QLQ-BN20). Adverse events (AEs) were evaluated using Common Terminology Criteria for AEs (CTCAE) v4.0.</p></sec><sec><title>Results</title><p>The PFS was 6.5 months in patients randomized to the treatment group with TTFields/TMZ combination <italic>versus</italic> 3.9 months in patients treated with TMZ monotherapy (HR, 0.47; 95% CI, 0.30–0.74; <italic>P</italic>=0.0236). The OS was 17.4 months in patients treated with TTFields/TMZ combination <italic>versus</italic> 13.7 months in patients treated with TMZ monotherapy (HR, 0.51; 95% CI, 0.33–0.77; <italic>P</italic>=0.0204). Annual survival rates with TTFields/TMZ <italic>versus</italic> TMZ monotherapy were 39% (95% CI, 29–50%) <italic>versus</italic> 27% (95% CI, 15–41%; <italic>P</italic>=0.072) at 2 years, 19% (95% CI, 11–29%) <italic>versus</italic> 11% (95% CI, 4–23%; <italic>P</italic>=0.135) at 3 years, and 15% (95% CI, 7–25%) <italic>versus</italic> 0% at 5 years, respectively. There were no significant differences between groups in the preselected items of HRQoL assessment. Grade ≥3 systemic AEs were 46% in the TTFields/TMZ group <italic>versus</italic> 40% in the TMZ monotherapy group, without statistically significant difference between the two groups. The only TTFields-related AEs were reversible scalp skin reactions, with grades 1–2 and grade 3 skin reactions reported by 51% and 2% of patients, respectively.</p></sec><sec><title>Conclusions</title><p>Combining TTFields with maintenance TMZ significantly improved PFS and OS in elderly patients with ndGBM in the phase 3 EF-14 clinical trial, without significant increases in systemic toxicity or negatively affecting patient HRQoL. TTFields-related skin AEs were low-grade and manageable.</p></sec><sec><title>Clinical Trial Registration</title><p><uri xlink:href="https://clinicaltrials.gov/ct2/show/NCT00916409" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/ct2/show/NCT00916409</uri>, identifier: NCT00916409.</p></sec>