Researchers found that armodafinil provides “no meaningful benefit” in reducing cancer-related fatigue among patients with high-grade glioma (HGG). These findings were published in JAMA Oncology.1
The researchers noted that nearly 96% of patients with HGG report moderate-to-severe fatigue, which is often underdiagnosed and undertreated. In a prior phase 2 trial, armodafinil improved fatigue for brain cancer patients with lower baseline fatigue scores.2
With this in mind, the researchers conducted a randomized, double-blind, placebo-controlled, phase 3 trial (ClinicalTrials.gov Identifier: NCT01781468) to determine whether armodafinil reduces fatigue in patients with grade 3-4 glioma who were clinically stable at least 4 weeks after completing radiation therapy.
The trial enrolled 328 patients, and they were randomly assigned to receive armodafinil (150 mg or 250 mg) or a placebo. There were 297 evaluable patients — 103 who received armodafinil at 150 mg, 97 who received armodafinil at 250 mg, and 97 who received placebo. Armodafinil and placebo were administered orally 4 times a day for 8 weeks.
Baseline characteristics were generally well balanced across the treatment arms. The exceptions were the brief fatigue inventory (BFI) usual level of fatigue in the past 24 hours and the BFI global fatigue score, both of which were higher in the armodafinil 250 mg arm than in the other arms.
There was no significant difference across the treatment arms in the proportion of patients who achieved the primary endpoint, which was clinically meaningful improvement in patient-reported fatigue. A clinically meaningful improvement was defined as at least a 2-point improvement in the BFI usual fatigue item at 8 weeks after treatment initiation.
From baseline to the end of week 8, the proportion of patients with a clinically meaningful improvement was 28% in the 150 mg armodafinil arm, 28% in the 250 mg armodafinil arm, and 30% in the placebo arm (P =.94).
There was no significant difference across the treatment arms when it came to the change in total Linear Analogue Self-Assessment score from baseline to the end of week 4 or the end of week 8.
Likewise, there was no significant difference across the arms in cognitive function tests from baseline to the end of week 4 or week 8.
Headache was the most common adverse event. It was slightly more common in the 250 mg armodafinil arm than in the 150 mg arm and the placebo arm — 47%, 40%, and 35%, respectively (P =.28).
There was a significantly higher rate of insomnia in the 250 mg arm compared with the 150 mg arm and the placebo arm — 7%, 2%, and 0%, respectively (P =.01).
Treatment discontinuation due to adverse events was reported in 14% of patients in the 250 mg arm, 8% of the 150 mg arm, and 4% of the placebo arm (P =.03).
“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,” the researchers concluded. “Unlike the study by Page et al,2 this study did not show any trend toward an improved response for those patients with worse baseline fatigue.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- 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. Published online December 9, 2021. doi:10.1001/jamaoncol.2021.5948
- 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