Antidepressant for Aromatase Inhibitor–Associated Arthralgia in Early-Stage Breast Cancer


Key Points

  • In women with early-stage breast cancer, duloxetine improved aromatase inhibitor–associated joint pain vs placebo.
  • Duloxetine was associated with a greater frequency of mostly grade 1 and 2 toxicities.

The phase III SWOG S1202 trial has shown benefit of the antidepressant agent duloxetine in reducing aromatase inhibitor–associated joint pain in women with early-stage breast cancer. These results were reported in the Journal of Clinical Oncology by Henry et al.

Study Details

In the double-blind trial, 299 aromatase inhibitor–treated postmenopausal women from 43 sites who had an average joint pain score of ≤ 4 out of 10 on the Brief Pain Inventory (BPI) that developed or worsened since aromatase inhibitor initiation were randomized between May 2013 and October 2015 to receive duloxetine (n = 150) or placebo (n = 149) for 13 weeks. Duloxetine was given at 30 mg in one capsule daily for 1 week followed by two 30-mg capsules daily for 11 weeks and then a taper of one capsule daily for 1 week. The primary endpoint was average joint pain through 12 weeks, with a multivariate analysis adjusting for the stratification factors of baseline pain score and prior taxane use. A clinically significant change in average pain was defined as a ≥ 2-point decrease from baseline.

Reduced Average Pain

Overall, 127 patients in the duloxetine group and 128 in the placebo group were evaluable for the primary analysis. At 12 weeks, the average pain score was reduced by 0.82 points more in the duloxetine vs placebo group (P = .0002). Similar patterns were observed for worst joint pain (1.06-point greater reduction, P < .001) and pain interference (0.95-point greater reduction, P < .001) on the BPI, as well as for improved joint stiffness (P = .0004) and improved functioning (P < .001) on other instruments. The proportions of patients with a ≥ 2-point improvement in average pain were 52% vs 40% at week 2 (P = .07), 68% vs 49% at week 6 (P = .003), and 68% vs 59% at week 12 (P = .18).

Adverse events of any grade occurred in 78% vs 50% of patients, with the most common in the duloxetine group being fatigue (32% vs 13%), nausea (30% vs 6%), dry mouth (25% vs 13%), and headache (21% vs 13%). No grade 4 adverse events were observed; grade 3 adverse events occurred in 9% vs 4%.

The investigators concluded: “Results of treatment with duloxetine for [aromatase inhibitor–associated musculoskeletal symptoms] were superior to those of placebo among women with early-stage breast cancer, although it resulted in more frequent low-grade toxicities.”

The study was supported by National Cancer Institute grants and by Lilly USA.

N. Lynn Henry, MD, PhD, of Huntsman Cancer Institute, University of Utah, is the corresponding author of the Journal of Clinical Oncology article.


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.