Treatment with armodafinil did not result in a significant difference in cancer-related fatigue between treatment arms for patients with high-grade glioma.
Use of armodafinil (Nuvigil) for patients with high-grade glioma did not help to reduce cancer-related fatigue, according to results from a phase 3 randomized trial (NCT01781468) published in JAMA Oncology.1
Investigators did not note any differences in fatigue reduction between the 150 mg arm (28%; 95% CI, 20%-30%), the 250 mg arm (28%; 95% CI, 19%-38%), and the placebo arm (30%; 95% CI, 21%-40%). A reduction in global fatigue was observed in patients treated with corticosteroids at –0.7 (95% CI, –1.5 to –0.3) compared with nonusers at -1.7 (95% CI, -2.1 to -1.3; P <.001).
“The results of this phase 3 randomized clinical trial, to our knowledge the largest of its kind designed to determine the effect of armodafinil in this setting, are consistent with prior studies regarding the use of armodafinil in this setting. Unlike the study by Page et al,2 this study did not detect any trend toward an improved response for those patients with worse baseline fatigue,” the investigators wrote.
A total of 328 patients were enrolled in this study, 297 of whom were evaluable. Baseline characteristics were well balanced between arms, except for brief fatigue inventory (BFI) usual fatigue level within 24 hours and BFI global fatigue scores. Treatment was completed by 195 patients, with 18% discontinuing due to withdrawal or refusal of continuation of treatment after initiation; this included 18% of patients in the 150 mg arm, 17% in the 250 mg arm , and 18% in the placebo arm. Discontinuation from adverse effects (AEs) occurred in 14% of patients in the 250 mg arm, 8% in 150 mg arm , and 4% in the placebo arm (P = .03).
Patients younger than 60 years experienced a larger mean change in BFI global fatigue score from baseline at –1.5 (95% CI, –2.0 to –1.1) compared with 0.9 (95% CI, –1.6 to –0.6; P = .02) in those who were 60 years or older at .
No statistically significant changes were observed in baseline Linear Analogue Self-Assessment score to week 4 or week 8 between treatment arms. Moreover, within the same time period, patients did not have a significant change in weekly leisure time activity score. A larger reduction in leisure time was seen at the end of week 4 at –3.3 (9% CI, –8.0 to 1.4) than at the end of week 8 at 1.2 (95% CI, –4.4 to 6.8; P = .04).
Additionally, investigators did not observe a major difference between treatment arms in terms of measuring cognitive function from baseline to weeks 4 and 8 Linear Analogue Self-Assessment score
z score change or amount of patients who experienced neurocognitive deterioration. At week 4, 36.6% (95% CI, 30.3%-43.2%) had a decline in cognitive function and 38.6% (95% CI, 31.5%-46.0%) declined at 8 weeks. In total, 37.7% (95% CI, 26.3%-50.2%) of those in the 250 mg arm had a neurocognitive decline at 4-weeks compared with 38.5% (95% CI, 27.7%-50.2%) in the 150 mg arm and 33.8% (95% CI, 23.6%-45.2%) in the placebo arm. At 8 weeks, the decline was 43.1% (95% CI, 30.9%-56.0%) in the placebo arm, 34.4% (95% CI, 22.7%-47.7%) in the 150 mg arm, and 37.9% (95% CI, 25.5%-51.6%) in the 250 mg arm.
Patients who had not previously underwent concomitant chemotherapy had a greater diminishment perceived cognitive impairment subscale score from baseline of 8.8 (95% CI, 4.9-12.6) compared with 4.5 (95% CI, 2.5-6.5) for those who had (P = .048).
AEs such as headache was the most common self-reported symptom in 41% (95% CI, 35%-47%; P = .28) of patients. In total, 47% (95% CI, 37%-57%) of patients in the 250 mg arm experienced headaches compared with 40% (95% CI, 31%-50%) in the 150 mg arm and 35% (95% CI, 26%-46%) in the placebo arm. The difference, however, was not statistically significant. Between the treatment arms, more patients reported insomnia in the 250 mg arm than the others.
1. Porter AB, Liu H, Kohli S, et al. Efficacy of treatment with armodafinil for cancer-related fatigue in patients with High-grade glioma: A phase 3 randomized clinical trial. JAMA Oncol. 2021;e215948. doi:10.1001/jamaoncol.2021.5948
2. Page BR, Shaw EG, Lu L, et al. Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiation-induced fatigue. Neuro-Oncol. 2015;17(10):1393-1401. doi:10.1093/neuonc/nov084