Abstract

BACKGROUND：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.

METHODS：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.

RESULTS：The PFS was 6.5 months in patients randomized to the treatment group with TTFields/TMZ combination versus 3.9 months in patients treated with TMZ monotherapy （HR, 0.47; 95% CI, 0.30-0.74; P=0.0236）. The OS was 17.4 months in patients treated with TTFields/TMZ combination versus 13.7 months in patients treated with TMZ monotherapy （HR, 0.51; 95% CI, 0.33-0.77; P=0.0204）. Annual survival rates with TTFields/TMZ versus TMZ monotherapy were 39% （95% CI, 29-50%） versus 27% （95% CI, 15-41%; P=0.072） at 2 years, 19% （95% CI, 11-29%） versus 11% （95% CI, 4-23%; P=0.135） at 3 years, and 15% （95% CI, 7-25%） versus 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 versus 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.

CONCLUSIONS：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.

CLINICAL TRIAL REGISTRATION：https://clinicaltrials.gov/ct2/show/NCT00916409, identifier: NCT00916409.

KEYWORDS：TTFields; Tumor Treating Fields; efficacy and safety; elderly patients; newly diagnosed glioblastoma; phase 3 clinical trial; quality-of-life; temozolomide.