Abstract P1-11-04: Association between body mass index (BMI) and response to duloxetine for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS)
Authors: Henry NL , Unger JM , Till C , Schott AF , Crew KD , Lew DL , Fisch MJ , Moinpour CM , Wade JL , Hershman DL 
Published: May 2019

Abstract
Background: AIMSS occurs often in women treated with AI therapy for early stage breast cancer and can negatively impact adherence and persistence with therapy. Duloxetine is a serotonin norepinephrine reuptake inhibitor used to treat mood disorders and chronic pain. In SWOG S1202, patients with AIMSS treated with duloxetine reported statistically significant improvement in pain by 12 weeks compared to placebo. Obesity is a predictor of increased likelihood of developing AIMSS, and a prior study of omega 3 fatty acid versus placebo for AIMSS showed a potential differential response to therapy by BMI. In this exploratory analysis of S1202, we investigated the association between baseline BMI and response to therapy.
Methods: In S1202, 299 postmenopausal women with stage I-III hormone receptor-positive breast cancer on AI therapy who developed new or worsening average pain of 4-10 on a numerical rating scale were enrolled, randomized 1:1 to duloxetine or placebo with randomization stratified by baseline pain (4-6 vs. 7-10) and prior taxane therapy (yes vs. no). Patients were treated for 12 weeks. Patient-reported outcomes including Brief Pain Inventory (BPI) were obtained at baseline and weeks 2, 6, 12, and 24. Patients were categorized into BMI&lt;30 kg/m2 (non-obese) or BMI≥30 kg/m2 (obese). The pre-specified aim of this secondary analysis was to examine whether the effect of intervention on BPI average pain at 12 weeks differed between obese and non-obese patients. Multiple linear regression was used, adjusting for the stratification factors and the baseline score. We tested whether the interaction of BMI status and intervention effect was statistically significant at α=.05.
Results: 289 patients were eligible for the analysis, 54% of whom were obese. The cohorts were well balanced other than by race. The difference by intervention arm in the 12-week mean BPI scores between baseline and follow-up scores was substantially different for the obese versus non-obese cohorts. In the patients with BMI&lt;30, the reduction in observed mean average pain score was similar in the duloxetine- and placebo-treated patients (-2.46 points vs. -2.34 points, p=.75). In contrast, in the patients with BMI≥30 the reduction in pain score was statistically significantly greater for the duloxetine-treated compared to the placebo-treated patients (-2.73 points vs. -1.64 points, p=.003; interaction p-value=.02). Differences in intervention effects between obese and non-obese groups were even stronger at 2-weeks (interaction p-value=.001) and 6-weeks (interaction p-value&lt;.0001). Similar findings were evident for other pain-related patient-reported outcomes.
Conclusions: In the placebo-controlled S1202 trial, obese patients with AIMSS obtained more analgesic benefit from duloxetine. Additional studies are warranted to determine the biologic basis for these findings, such as a different mechanism underlying development of AIMSS or pain expression in patients with obesity, or other confounding variables related to analgesic response to duloxetine relative to placebo.
Support: NIH/NCI grants CA189974, CA189821, CA180820; and in part by Damon Runyon-Lilly Clinical Investigator Award #CI-53-10 [to NLH], and in part by Lilly USA, LLC.
Citation Format: Henry NL, Unger JM, Till C, Schott AF, Crew KD, Lew DL, Fisch MJ, Moinpour CM, Wade JL, Hershman DL. Association between body mass index (BMI) and response to duloxetine for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-04.