In a phase III trial reported in JAMA Oncology, Porter et al found that armodafinil, a psychostimulant, did not improve cancer-related fatigue vs placebo in adult patients with high-grade glioma.
As stated by the investigators, “Nearly 96% of patients with high-grade glioma report moderate-to-severe fatigue.”
Study Details
The U.S. multicenter double-blind trial included 297 evaluable patients with moderate-to-severe fatigue who were clinically stable at ≥ 4 weeks after completing radiation therapy. They were randomly assigned 1:1:1 between June 2013 and December 2019 to receive armodafinil at 150 mg four times daily (n = 103), armodafinil at 250 mg four times daily (n = 97), or placebo (n = 97) for 8 weeks. Moderate-to-severe fatigue was defined as a score of ≥ 6 out of 10 on the Brief Fatigue Inventory (BFI) scale. Clinically meaningful improvement in fatigue was defined as a reduction of two points on the BFI scale from baseline. Patients were allowed to receive stable doses of corticosteroids but were excluded if they required an increased corticosteroid dose, were receiving another treatment for fatigue, or had an uncontrolled seizure disorder.
Key Findings
Proportions of patients achieving clinically meaningful reductions in fatigue from baseline after 8 weeks were 28% (95% confidence interval [CI] = 20%–30%) in the 150-mg group, 28% (95% CI = 19%-38%), in the 250-mg group, and 30% (95% CI = 21%–40%) in the placebo group (overall P = .94).
Totals of 38.1% to 40.8% of patients in the three groups were receiving corticosteroids. Totals of 46.6% to 50.5% were aged < 60 years. Among all patients, analysis of mean change in BFI global fatigue score from baseline showed reductions of −0.7 (95% CI = −1.5 to −0.3) among corticosteroid users vs −1.7 (95% CI = −2.1 to −1.3) among nonusers (P < .001) and reductions of −1.5 (95% CI = −2.0 to −1.1) among patients aged < 60 years vs −0.9 (95% CI = −1.6 to −0.6) among older patients (P = .02).
Headache of any grade was the most common adverse event among all patients, occurring in 40.0% of the 150-mg group, 47% of the 250-mg group, and 35% of the placebo group (overall P = .28). Insomnia was reported by seven patients in the 250-mg group vs two in the 150-mg group.
The investigators concluded, “The results of this randomized clinical trial found no meaningful benefit of using treatment with armodafinil to reduce cancer-related fatigue in patients with high-grade glioma.”
Alyx B. Porter, MD, of Mayo Clinic, Phoenix, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
