Influence of Treatment With Tumor-Treating Fields on Health-Related Quality of Life of Patients With Newly Diagnosed Glioblastoma: A Secondary Analysis of a Randomized Clinical Trial

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Taphoorn has performed paid consultancy for Hoffmann-La Roche. Dr Lavy-Shahaf is an employee of and received personal fees from Novocure during the conduct of the study. Drs Weinberg and Kirson are employees of and own minority stock in Novocure. Dr Taillibert received fees from Centre-de-Recherche-en-Neuro-Oncologie for enrolling patients at Salpêtrière University Hospital during the conduct of the study. Dr Idbaih received research support from Foundation ARC, IntselChimos, Beta-Innov, and Carthera and travel support from Carthera and Hoffmann-La Roche and served as a paid member of the advisory boards of BMS, Hoffmann-La Roche, and Lettre du Cancérologue. Dr Hottinger received research support from Novocure and served on advisory boards of Servier and BMS (fees paid to the institution). Dr Roth served as a paid member of the advisory boards of Roche and MSD and received personal fees for lectures on behalf of BMS and Novocure. Dr Ram received grants and personal fees from and owns minority stock in Novocure. Dr Stupp received nonfinancial support from Novocure, and his institution received fees from Celgene, Novartis, AbbVie, Merck KGaA (Darmstadt), and MSD-Merck & Co. Dr Stupp’s spouse is a full-time employee of Celgene. No other conflicts were reported.

Figures

Figure 1.. CONSORT Diagram

Data are the number and percentage of patients in the categories (baseline, alive, and progression-free) who completed the health-related quality-of-life (HRQoL) questionnaire at the indicated times. pts indicates patients; TTFields, tumor-treating fields.

Figure 2.. Changes in Global Health Status and Itchy Skin

Mean changes in points on health-related quality of life scales from baseline in global health status (A) and itchy skin with (B) with tumor-treating fields (TTFields) plus temozolomide compared with temozolomide alone. No change, between 0 and 10 points; improvement and deterioration, changes of 10 points or more. Error bars indicate SD.

Figure 3.. Deterioration-Free Survival and Time to Deterioration

Deterioration-free survival (A) and time to deterioration (B) for health-related quality-of-life domains in patients who received tumor-treating fields (TTFields) plus temozolomide compared with temozolomide alone. HR indicates hazard ratio.