The STAMPEDE trial began in 2005 to assess novel approaches for patients with prostate cancer starting long-term androgen deprivation therapy (ADT) for the first time. Long-term ADT is recommended for patients with metastatic hormone-sensitive prostate cancer (mHSPC), but bone loss and increased risk of fractures are known complications.
Among other approaches, the STAMPEDE trial examined the addition of zoledronic acid (ZA), docetaxel, or both to ADT for the treatment of mHSPC. Details of this trial were presented at the American Urological Association 2023 Annual Meeting.
Hospital Episode Statistics (HES) data up to 2018 were obtained for 2145 eligible patients who were randomized 2:1 between ADT (Arm A) and ADT plus ZA (Arm B), ADT plus docetaxel (Arm C), or ADT plus docetaxel and ZA (Arm E). ZA (4 mg) was administered in 6 3-weekly cycles followed by 4-weekly cycles for 2 years.
Clinical fracture events were measured using a prespecified coding framework of International Classification of Diseases, 10th Revision diagnosis and Office of Population Censuses and Surveys Classification of Interventions and Procedures procedure codes. Multivariate Cox regression models were developed to adjust for age, N stage, World Health Organization performance status, Gleason score, and nonsteroidal anti-inflammatory drug use to determine the impact of ZA on fracture risk.
Accessible, high-quality, routinely collected health care data (RCHD) enabled analysis of outcome data beyond standard trial follow-up to evaluate the long-term treatment toxicity and clinical efficacy of ZA as a bone-protective agent in mHSPC. The HES database provided RCHD for the patients taking part in the study.
The 5-year fracture incidence among the patient group was 6.4%. It was higher in M1 patients (9.6% in M1 vs 2.1% in M0; P<.0001) and lower among M1 patients allocated ZA (4.55% with ZA vs 12.90% without ZA; P<.0001). ZA significantly reduced fracture risk in M1 patients (hazard ratio [HR], 0.36; 95% CI, 0.22-0.57; P<.0005) but not in M0 patients (HR, 0.67; 95% CI, 0.32-1.39; P=.28).
Using RCHD, researchers evaluated long-term fracture events among patients taking part in the STAMPEDE trial. Fracture rates were clinically notable in patients with M1 disease and reduced significantly in patients who were administered ZA with ADT with or without docetaxel, supporting the use of bone-protective agents to reduce clinically significant fractures in mHSPC.