The use of duloxetine resulted in reduced aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) compared with placebo in women with early-stage breast cancer, according to a new study. However, the agent did result in more low-grade toxicity.
“Treatment with an AI for 5 years reduces 10-year breast cancer mortality by about 40%. However, approximately half of patients develop bothersome AIMSS, including joint pain and stiffness, and 20% to 30% discontinue treatment early because of intolerance,” wrote study authors led by N. Lynn Henry, MD, PhD, of the University of Utah Huntsman Cancer Institute in Salt Lake City.
Duloxetine, a serotonin–norepinephrine reuptake inhibitor, is indicated for depression and anxiety, but also for treatment of multiple chronic pain conditions, including fibromyalgia and chronic musculoskeletal pain. The investigators conducted a randomized phase III trial comparing duloxetine (127 patients) with placebo (128 patients) in postmenopausal women with early breast cancer undergoing AI treatment. The results were published in the Journal of Clinical Oncology.
The median age of patients was 60 years, most were white (86%), and most had an ECOG performance status of 0 (68%). Self-reported baseline pain scores were 4 to 6 in 76% of patients, and 7 to 10 in 24%. A majority of the cohort (64%) had been on AI therapy for less than 1 year; 28% had been on an AI for 1 to 2 years, and 9% for 2 to 3 years.
Within 12 weeks of therapy, the average joint pain score was 0.82 points lower with duloxetine compared with placebo (P = .0002). Patients’ worst joint pain scores were 1.06 points lower with duloxetine (P < .001). Significant reductions in average pain scores were seen at each time point between 2 and 12 weeks. At week 24, 12 weeks following the completion of the duloxetine or placebo treatment, there was no difference between the groups (P = .80).
Duloxetine patients were also more likely to have a clinically meaningful improvement in pain, defined as at least a 2-point improvement, by week 6 (68% vs 49%; P = .003). Again, by week 24, the rates were similar.
Secondary endpoints were also better with duloxetine. Measures of functioning, pain, and stiffness for knees and hips, as well as for hands, saw significant improvement with the study drug.
Adverse events were more frequent in the duloxetine patients, occurring in 78% compared with 50% of placebo patients (P < .001). Grade 3 adverse events were reported by 17 patients (12 duloxetine patients and 5 placebo patients; P = .08). The most common adverse events with duloxetine included fatigue, nausea, dry mouth, and headache; with placebo, the most common were fatigue, dry mouth, and headache.
“Considering the high incidence of bothersome and intolerable musculoskeletal toxicity in AI-treated women, as well as the paucity of interventions with proven benefit, this trial provides important findings about a new treatment option for women with AIMSS,” the authors concluded. “These results support consideration of a short course of duloxetine in symptomatic patients to assess improvement in AIMSS and tolerance of duloxetine.”