The addition of tumor-treated fields to standard therapy with temozolomide prolonged deterioration-free survival without negatively influencing health-related quality of life among patients with glioblastoma, according to a secondary analysis of a phase 3 clinical trial published in JAMA Oncology.
However, tumor-treating fields, or TTFields (Optune, Novocure) — alternating electrical fields delivered via four transducer arrays at an intermediate frequency of 200 MHz (1-3 V/cm) placed on the shaved scalp of patients and connected to a portable medical device — also caused skin irritation in more than half of patients.
“As expected, itchy skin was reported more frequently [among] patients treated with TTFields because of the transducer arrays that have to be placed on the scalp of the patient,” Martin J.B. Taphoorn, MD, PhD, professor of neurology at Haaglanden Medical Center in the Netherlands, and colleagues wrote. “Combining the results of the survival and health-related quality of life analyses suggests that the addition of TTFields to adjuvant temozolomide is of value to patients with glioblastoma.”
Glioblastoma has a poor prognosis and, as tumors grow, patients often experience a progressive decline in neurologic function and health-related quality of life. Current standard of care for newly diagnosed glioblastoma includes surgical resection followed by radiotherapy with concomitant and maintenance chemotherapy with temozolomide.
As HemOnc Today previously reported, patients treated with TTFields demonstrated superior PFS (6.7 months vs. 4 months; HR = 0.63; P = .00005) and median OS (20.9 months vs. 16 months; HR = 0.63; 95% CI, 0.53-0.76) compared with those treated with temozolomide alone.
In a secondary analysis of that EF-14 randomized study, Taphoorn and colleagues evaluated the addition of TTFields to temozolomide among 695 patients with glioblastoma after completion of radiochemotherapy from July 2009 until November 2014. Researchers followed patients through December 2016.
Patients received temozolomide (150 mg/m2 to 200 mg/m2 per day) for 5 days during each 28-day cycle. Patients assigned TTFields were advised to continue treatment for at least 18 hours per day.
Time to deterioration served as the primary endpoint. Health-related quality of life — measured with questionnaires at baseline and every 3 months thereafter — served as a secondary endpoint.
Of those evaluated, 639 patients (91.9%; 68.4% men; mean age, 54.8 years) completed the baseline health-related quality-of-life questionnaire.
Health-related quality of life did not differ significantly between treatment arms, except for itchy skin, which occurred among 52% of participants (2% reported severe skin irritation). Deterioration-free survival appeared significantly longer with TTFields for global health (4.8 months vs. 3.3 months); physical (5.1 months vs. 3.7 months) and emotional functioning (5.3 months vs. 3.9 months; pain (5.6 vs. 3.6 months); and leg weakness (5.6 vs. 3.9 months; P < .01 for all), likely related to improved PFS.
Time to deterioration worsened with TTFields for itchy skin (8.16 months vs. 14.4 months; HR = 1.85; 95% CI, 1.33-2.57), but improved for pain (13.37 months vs. 12.13 months; HR = 0.65; 95% CI, 0.48-0.89). Time to deterioration of role, social and physical functioning did not appear different between the arms.
Researchers noted missing health-related quality-of-life data during follow-up — 65.8% of patients had assessments at 3 months, and 41.7% at 12 months — as a limitation to their study.
“However, it is unlikely that these factors influenced our conclusion, as the objective of this study was to compare health-related quality-of-life results between two treatment arms in which patients were similar due to randomization,” Taphoorn and colleagues wrote.
Low adherence to health-related quality-of-life assessment at 3 and 12 months is a difficulty of this study, Lia M. Halasz, MD, associate professor of radiation oncology at University of Washington School of Medicine, and Timur Mitin, MD, PhD, assistant professor of radiation medicine at Oregon Health & Science University, wrote in an accompanying editorial.
“It is comforting to learn that the burden of carrying the device was not detrimental to patients’ physical, social or emotional functioning,” Halasz and Mitin wrote. “However, overall it is important to remember that the trial participants were a highly selective group of patients.”
Because the individuals selected to take part in the trial agreed to wear a device on their scalp daily for an indefinite time, they may not represent the majority of patients with glioblastoma, according to Halasz and Mitin.
“In our experience, there are many social and cultural reasons that patients have for declining TTFields despite the data of improved survival,” they wrote. “Many do not want the physical and visual cues that may remind them of their life-altering, life-limiting diagnosis. This factor may echo studies finding that patients with breast cancer rate alopecia as one of the most distressing treatment-related adverse effects because it can result in anxiety, depression, negative body image, lowered self-esteem and reduced sense of well-being.
“With societal changes and the greater acceptability of wearable devices, ranging from fitness trackers to assistive technology, it will be interesting to see if patients become more open to utilizing TTFields,” they added. – Chuck Gormley
Disclosures: Novocure Ltd. funded the study. Taphoorn reports a consultant role with Hoffman-La Roche. Mitin reports clinical funding from Novocure. Please see the full study for all other authors’ relevant financial disclosures.