Utilization patterns of oral therapies in prostate cancer in Tuscany: a retrospective observational study based on regional administrative databases

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Other
• If ‘other’, further details on the scope of the study:
  descriptive safety study
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  DAROLUTAMIDE

  ENZALUTAMIDE

  APALUTAMIDE

  ABIRATERONE ACETATE
• Anatomical Therapeutic Chemical (ATC) code:
  (L02BX03) abiraterone

  abiraterone

  (L02BB05) apalutamide

  apalutamide

  (L02BB04) enzalutamide

  enzalutamide

  (L02BB06) darolutamide

  darolutamide
• Medical condition to be studied:
  Prostate cancer

Population studied

• Short description of the study population:
  All individuals residing in Tuscany, registered with the Regional Healthcare Service, aged ≥18 years, and with at least one dispensing of one of the drugs of interest (Table A) between 1 January 2016 and 31 December 2025 (i.e., the index drug) will be included. The cohort entry date (index date) will correspond to the dispensing date of the index drug. Individuals aged <18 years at the index date will be excluded to avoid including patients who received these treatments for indications other than prostate cancer. In addition, individuals with less than 24 months of available observation in the regional healthcare registry before the index date will be excluded. Three categories of users will be identified:; 1) First-line users: patients with a dispensing of the index drug and no dispensing of any other drug of interest during the 24 months preceding the index date;; 2) New users beyond first-line therapy: patients with at least one dispensing of the index drug and at least one previous dispensing of another drug of interest, excluding the index drug, during the 24 months preceding the index date;; 3) Prevalent users: patients with at least one dispensing of one of the drugs of interest and at least one dispensing of the same drug during the 24 months preceding the index date.; Patients will be identified based on the first dispensing of the study drugs recorded in the regional administrative FED and SPF databases using Anatomical Therapeutic Chemical (ATC) codes (Table A). Follow-up for each patient will begin on the index date and will end on 31 December 2025, or on the date of death, transfer outside the Tuscany Region, loss to follow-up, discontinuation of the index drug, or switching to another antineoplastic drug other than the index drug, whichever occurs first. Treatment discontinuation and treatment switching will be defined according to the criteria described in the "Variables" section. Treatment discontinuation and switching events will be assessed during the 12 months following the index date.; Among patients receiving one of the drugs of interest, selected clinically relevant events (cardiovascular events, renal impairment, hepatic impairment, and fractures) will also be identified according to diagnoses recorded in the Hospital Discharge Records (HDR) and Emergency Department (ED) databases during the 12 months following the index date (Table B);

Study design details

• Study design:
  This study will be a retrospective, descriptive observational study based on the identification of a cohort of patients treated with abiraterone, apalutamide, enzalutamide, or darolutamide in each year of the study period, using data extracted from the Tuscan administrative healthcare databases
• Main study objective:
  to describe the use of the main oral therapies for prostate cancer in the region, with particular focus on the introduction of second-generation androgen receptor inhibitors compared with abiraterone. In particular, the descriptive comparison between abiraterone and second-generation androgen receptor inhibitors may provide useful insights into how the introduction of new therapeutic options has changed the management of prostate cancer in Tuscany and whether this has occurred uniformly or differently across the various regional areas.
• Setting:
  The study will exclusively use the regional administrative healthcare databases of Tuscany, whose data are routinely collected for administrative purposes and allow the identification of healthcare services provided to individuals covered by the Tuscan Regional Healthcare Service.
• Comparators:
  Previously most widely used therapy (abiraterone)
• Outcomes:
  Primary endpoints:; ● Description of the use of the main oral therapies for prostate cancer in routine clinical practice in Tuscany, with particular focus on the use of abiraterone, apalutamide, enzalutamide, and darolutamide during the study period (2016–2025).; ● Description of the distribution of patient categories (first-line users, new users beyond first-line therapy, and prevalent users) for each study drug by calendar year and Regional Healthcare Area (Area Vasta) of Tuscany.; ● Description of the demographic (age, sex, and area of residence) and clinical (comorbidities and concomitant treatments) characteristics of patients treated with the oral therapies of interest for prostate cancer during the study period (2016–2025).; ● Description of the frequency of treatment discontinuation and treatment switching among patients treated with abiraterone, apalutamide, enzalutamide, and darolutamide.; Secondary endpoint; • Description of the occurrence of major cardiovascular events and other clinically relevant events during the follow-up period;
• Data analysis plan:
  The analyses will be primarily descriptive. Categorical variables will be summarized as absolute frequencies and percentages, while continuous variables will be described using the mean and standard deviation or the median and interquartile range, according to the distribution of the data.; The following will be described:; A. The percentage of first-line users, new users beyond first-line therapy, and prevalent users among all users of each drug of interest, by calendar year (2016–2025) and Local Health Authority of residence (Figures 1a–d);; B. The percentage of first-line users receiving each of the four drugs of interest among all first-line users, by Local Health Authority of residence and calendar year (2016–2025) (Figure 2);; C. The demographic and clinical profile (comorbidities and concomitant pharmacological treatments) of first-line users and new users beyond first-line therapy during the periods 2016-2019, 2020-2022, 2023-2025, on the basis of the patients’ cohort entry, by drug of interest and Local Health Authority of residence (Tables 1a–d);; D. The frequency of treatment discontinuation and switching from the index drug to one of the other drugs of interest among first-line users and new users beyond first-line therapy during the 12 months following the index date, by drug of interest and Local Health Authority of residence (Tables 1a–d); E. The frequency of safety events of interest across the different treatment groups classified according to treatment line (first-line users and new users beyond first-line therapy) (Table 2). Specifically, the adverse events listed in Table 2 will be evaluated among patients receiving the drug of interest, who will be followed for up to 12 months from the dispensing date of the index drug or until death, treatment discontinuation, treatment switching, or loss to follow-up (removal from the regional healthcare registry), whichever occurs first.; Sensitivity analysis; - Treatment discontinuation and switching from the index