Abstract

IMPORTANCE：Tumor-treating fields （TTFields） therapy improves both progression-free and overall survival in patients with glioblastoma. There is a need to assess the influence of TTFields on patients’ health-related quality of life （HRQoL）.

OBJECTIVE：To examine the association of TTFields therapy with progression-free survival and HRQoL among patients with glioblastoma.

DESIGN, SETTING, AND PARTICIPANTS：This secondary analysis of EF-14, a phase 3 randomized clinical trial, compares TTFields and temozolomide or temozolomide alone in 695 patients with glioblastoma after completion of radiochemotherapy. Patients with glioblastoma were randomized 2:1 to combined treatment with TTFields and temozolomide or temozolomide alone. The study was conducted from July 2009 until November 2014, and patients were followed up through December 2016.

INTERVENTIONS：Temozolomide, 150 to 200 mg/m2/d, was given for 5 days during each 28-day cycle. TTFields were delivered continuously via 4 transducer arrays placed on the shaved scalp of patients and were connected to a portable medical device.

MAIN OUTCOMES AND MEASURES：Primary study end point was progression-free survival; HRQoL was a predefined secondary end point, measured with questionnaires at baseline and every 3 months thereafter. Mean changes from baseline scores were evaluated, as well as scores over time. Deterioration-free survival and time to deterioration were assessed for each of 9 preselected scales and items.

RESULTS：Of the 695 patients in the study, 639 （91.9%） completed the baseline HRQoL questionnaire. Of these patients, 437 （68.4%） were men; mean （SD） age, 54.8 （11.5） years. Health-related quality of life did not differ significantly between treatment arms except for itchy skin. Deterioration-free survival was significantly longer with TTFields for global health （4.8 vs 3.3 months; P < .01）; physical （5.1 vs 3.7 months; P < .01） and emotional functioning （5.3 vs 3.9 months; P < .01）; pain （5.6 vs 3.6 months; P < .01）; and leg weakness （5.6 vs 3.9 months; P < .01）, likely related to improved progression-free survival. Time to deterioration, reflecting the influence of treatment, did not differ significantly except for itchy skin （TTFields worse; 8.2 vs 14.4 months; P < .001） and pain （TTFields improved; 13.4 vs 12.1 months; P < .01）. Role, social, and physical functioning were not affected by TTFields.

CONCLUSIONS AND RELEVANCE：The addition of TTFields to standard treatment with temozolomide for patients with glioblastoma results in improved survival without a negative influence on HRQoL except for more itchy skin, an expected consequence from the transducer arrays.

TRIAL REGISTRATION：clinicaltrials.gov Identifier: NCT00916409.