BACKGROUND: The β3-adrenergic agonist mirabegron is an alternative to antimuscarinics (AMs) for treatment of overactive bladder. During mirabegron development, a greater number of cancers were observed in mirabegron than tolterodine/placebo patients.
OBJECTIVES: This post-authorization safety study was designed to generate additional evidence related to this observation and compared incidence of sex-specific composite cancer outcomes (first occurrence of cancer of the lung/bronchus, colon/rectum, melanoma of skin, urinary bladder, non-Hodgkin’s lymphoma, kidney/renal pelvis, pancreas [prostate in men and breast/corpus uteri in women]) in patients prescribed/dispensed mirabegron vs AMs. Comparisons were made overall and for person-time in the 1 year and >1 year following start of treatment, for all ages and for a subgroup ≥65 years.
METHODS: Cohorts of mirabegron initiators were matched using propensity scores to AM initiators within real-world data sources (Danish National, Swedish National, Clinical Practice Research Datalink [UK], Optum Research [US], Humana [US]). Between 2012 and 2018, cancer cases occurring during cohort follow-up were identified from direct linkage to cancer registries or validated through medical record review or physician questionnaires.
RESULTS: Among the 80,637 mirabegron initiators matched to 169,885 AM initiators, 68% were ≥65 years of age and 66% were women. Follow-up of these cohorts identified 5,835 cancer cases. Incidence rates (IRs) were higher for men than women for composite and individual cancer outcomes; there was no appreciable heterogeneity of cancer incidence across specific AM medications. The pooled fixed effects HR for composite cancer outcomes (all ages) was 1.05 (95% CI: 0.98, 1.14) for women and 1.06 (95% CI: 0.98, 1.14) for men. Results were similar in persons ≥65 years. IRs for bladder and prostate cancers were higher in both mirabegron and AM cohorts in the first 6 months after treatment initiation, suggesting protopathic bias.
CONCLUSIONS: This large multi-country real-world study, with up to 6 years of follow up, found no evidence of an association between mirabegron use and risk of the studied cancers, compared to AMs, in either men or women.
