The impact of cannabidiol (CBD) on aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS).

e24060 Background: Although treatment with an AI for 5-10 years decreases 10-year breast cancer (BC) mortality by about 40%, up to 25% of patients will stop treatment early because of treatment-related, intolerable joint and muscle pain and stiffness, called AIMSS. Only acupuncture, duloxetine, and exercise have been shown to reduce AIMSS. While the exact underlying mechanism is unknown, it is thought to be due in part to ongoing systemic inflammation. CBD has anti-nociceptive and anti-inflammatory properties, making it a potential treatment option for AIMSS. Methods: Women with stage 0-3 hormone receptor-positive BC experiencing AIMSS (defined as worst joint pain ≥4/10 during prior 7 days that developed or worsened since starting AI therapy) were eligible for enrollment in this single arm, single center phase 2 open label clinical trial (NCT04754399). Patients received an FDA-approved formulation of CBD (Epidiolex), titrated over 4 weeks from 25 mg BID to 100 mg BID and then continued at maximum tolerated dose for a total of 15 weeks. Patient-reported outcomes (PRO) data were collected serially, including the Brief Pain Inventory (BPI) and the PROMIS Profile 29+2 v2.1. The primary endpoint was the number of CBD-treated patients with at least a 2-point reduction (minimal clinically important difference) in worst pain from baseline to 15 weeks. Statistical analysis was completed using paired t-tests and linear mixed models. Results: Of 39 eligible patients (Table 1), 11 discontinued participation early due to patient discretion (n = 6) or adverse event (n = 5). There were no grade 3-4 toxicities. Analyzing data from all 39 patients, there was an improvement in BPI worst pain (0-10 scale) of 0.13 per week of treatment after baseline (p < 0.001), resulting in an average improvement in worst pain of 1.95 at the end of 15 weeks. Of the 28 patients who completed the study, 17 (60.7%) reported a ≥2-point improvement in BPI worst pain between baseline and week 15. There was a significant improvement in PROMIS T score at week 15 in both physical function (2.34, p = 0.01) and ability to participate in social roles and activities (2.71, p = 0.02). Conclusions: Treatment with CBD was associated with an improvement in joint pain for a subset of patients. Additional analyses are ongoing to further investigate the impact of CBD on AIMSS and to explore which patients are most likely to benefit from treatment with CBD. Clinical trial information: NCT04754399 . Table: see text