Phase II randomised placebo-controlled trial of melatonin for the management of sleep disturbance in women with early breast cancer on adjuvant endocrine therapy.

Abstract

e12533 Background: Sleep disturbance is common among women on endocrine therapy for early breast cancer. This study investigated the effect of prolonged-release melatonin on sleep disturbance in women with early breast cancer on adjuvant endocrine therapy. Methods: In a multi-centre, randomised, double-blind, placebo-controlled Phase 2 trial, women with stage I-III breast cancer on adjuvant endocrine therapy experiencing sleep disturbance defined by Pittsburgh Sleep Quality Index (PSQI) score ≥5, were randomised 2:1 to receive prolonged-release melatonin 2mg or placebo daily for 12 weeks. Participants completed: Patient Reported Outcome Measures (PROMs) at baseline, week 6, 12 and 24; actigraphy at baseline and week 12. The primary endpoint was the effect of melatonin on sleep quality (proportion of women with ≥ 3-point decrease in PSQI score from baseline to week 12). Analyses were on an intention-to-treat basis. All statistical tests were two-sided. Results: Between September 2022 and July 2025, 53 participants were recruited and randomly assigned to melatonin (n = 36) or placebo (n = 17), with a mean age of 56 years (SD 9.1, range 39-79); most had stage one (42%) or two (42%) disease; 33% on tamoxifen; 67% aromatase inhibitor; 19% ovarian function suppression; 45% had received adjuvant chemotherapy. The baseline PSQI score was 11.6 (SD 3.3). The proportion achieving a ≥3 point decrease in PSQI score at week 12 compared to baseline was 55% (17/31) in the melatonin group and 46% (6/13) in the placebo group (p = 0.6). There was no significant difference in the number of poor sleepers (PSQI ≥5) for melatonin at baseline 97% (35/36) and week 12 81% (26/34), versus placebo 100% (17/17) and 100% (13/13) respectively ( p = 0.3); or the mean PSQI score for melatonin at baseline, 11.6 (SD 3.3) and week 12, 8.16 (SD 3.1), versus placebo 11.4 (SD 3.3) and 8.1 (SD 3.1) respectively ( p = > 0.05). Overall, the mean FACT-ES total score and FACT-F subscale score for the total group significantly improved from baseline to week 6, 12 and 24 ( p = < 0.001); however, there was no significant difference between melatonin and placebo ( p = > 0.05). One patient (3%) receiving melatonin reported a grade 3 treatment-related adverse event, with headache leading to study drug discontinuation. Conclusions: Prolonged-release melatonin did not improve sleep quality compared with placebo in women with early breast cancer on adjuvant endocrine therapy. Although the trial did not meet its primary endpoint, the findings provide important insights into the management of sleep disturbance in this population. Clinical trial information: ACTRN12619001284156.