To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression.
Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1-24 months). AUR/S incidence was described by Kaplan-Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment.
Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p < 0.001) were observed when switch to CT occurs ≥ 6 months from the initial treatment. At month 48, AUR/S incidence was 4.6% vs 9.5%, 11.0% and 11.3% in patients receiving immediate CT vs. switchers after 6, 12 and 24 months, respectively.
Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression.
World journal of urology. 2020 Dec 18 [Epub ahead of print]
Salvatore D'Agate, Chandrashekhar Chavan, Michael Manyak, Juan Manuel Palacios-Moreno, Matthias Oelke, Martin C Michel, Claus G Roehrborn, Oscar Della Pasqua
Clinical Pharmacology and Therapeutics Group, University College London, BMA House, Tavistock Square, London, WC1H 9JP, UK., Global Medical Urology, GlaxoSmithKline, Mumbai, India., Global Medical Urology, GlaxoSmithKline, Philadelphia, USA., Global Medical Urology, GlaxoSmithKline, Tres Cantos, Spain., Department of Urology, St. Antonius Hospital, Gronau, Germany., Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany., Department of Urology, Texas Southwestern Medical Center, Dallas, TX, USA., Clinical Pharmacology and Therapeutics Group, University College London, BMA House, Tavistock Square, London, WC1H 9JP, UK. .