Q-122 as a novel, non-hormonal, oral treatment for vasomotor symptoms in women taking tamoxifen or an aromatase inhibitor after breast cancer: a phase 2, randomised, double-blind, placebo-controlled trial

Q-122 as a novel, non-hormonal, oral treatment for vasomotor symptoms in women taking tamoxifen or an aromatase inhibitor after breast cancer: a phase 2, randomised, double-blind, placebo-controlled trial

Background

Vasomotor symptoms (VMS; hot flushes and night sweats) are experienced by over two-thirds of women with breast cancer taking oral adjuvant endocrine therapy. Safe and effective treatments are lacking. Q-122 is a novel non-hormonal compound that has shown promise for reducing VMS by modulation of oestrogen-responsive neurons in the hypothalamus.

Methods

We conducted a phase 2, randomised, double-blind, placebo-controlled trial of the effectiveness of Q-122 for VMS. Eligible participants were women, aged 18 to 70 years, taking a stable dose of tamoxifen or an aromatase inhibitor following breast cancer and experiencing at least 50 self-reported moderate to severe VMS per week. Participants were randomly allocated to oral Q-122 100 mg or identical placebo, twice daily for 28 days. The primary outcome was the difference in the mean percentage change from baseline in the VMS Severity Score of moderate and severe hot flushes and night sweats (msVMS-SS) between Q-122 and placebo after 28 days of treatment. The impact of VMS on quality of life was assessed using the Hot Flash Related Daily Interference Scale (HFRDIS). Analysis was by modified intent-to-treat and safety population. The study is registered at ClinicalTrials.gov, NCT03518138.

Findings

Of the 243 participants screened, 131 were randomised and received treatment between October 24, 2018 and September 9, 2020; 65 randomized to Q-122 and 66 to placebo. Q-122 significantly reduced msVMS-SS compared with placebo (least squares mean: Q-122, -39% [95% CI -46, -31] vs placebo -26% [-33, -18], p=0·018). Q-122 resulted in significant improvements in the HFRDIS subdomains of sleep (p=0·029), social (p=0·030), and leisure activities (p=0·025). Treatment emergent adverse events were generally mild to moderate with no serious adverse events.

Interpretation

Q-122 is an effective and well tolerated non-hormonal oral treatment for VMS in women taking oral adjuvant endocrine therapy after breast cancer. The results support the conduct of larger and longer studies of Q-122, with potential use extending to postmenopausal women who require an alternative to menopausal hormone therapy.