Bisphosphonates May Reduce Fracture Risk in Patients With Metastatic Hormone-Sensitive Prostate Cancer

Bisphosphonates May Reduce Fracture Risk

An analysis of patients who participated in the phase 2/3 STAMPEDE trial (NCT00268476) suggest that bisphosphonates such as zoledronic acid can significantly reduce the risk of fracture in patients with metastatic hormone-sensitive prostate cancer (mHSPC).¹

Results presented at the 2023 AUA Annual Meeting showed that, among patients with metastatic disease, the use of zoledronic acid led to a 64% reduction in fracture risk (HR, 0.36; 95% CI, 0.22-0.57, P <.0005). In patients with non-metastatic disease, however, there was not a significant association between the use of zoledronic acid and a reduction in the risk of fracture (HR, 0.67; 95% CI, 0.32-1.39; P = .28).

In an interview with Oncology Nursing News at the AUA meeting, lead study author Craig Jones, MBChB, a urology SpR at Christie and Salford Royal NHS Foundation, in England, highlighted the significance of the findings.

“The fracture incidence in metastatic patients was high across all patients randomized in the original STAMPEDE trial and when we stratified patients by whether or not they received zoledronic acid in the original study, it showed that zoledronic acid significantly reduced the risk of fracture, with a hazard ratio of 0.36.”

STAMPEDE included 2962 men with high-risk, locally advanced, metastatic or recurrent prostate cancer initiating first-line long-term androgen deprivation therapy (ADT).2 Patients were randomized to ADT alone, ADT plus zoledronic acid, ADT plus docetaxel, or ADT plus zoledronic acid and docetaxel. The overall study findings showed that zoledronic acid did not improve overall survival outcomes.

The researchers undertook this study to assess the long-term impact of bisphosphonate treatment on patients’ skeletal health. Using the Hospital Episode Statistics (HES) database, the investigators accessed routinely-collected healthcare data (RCHD) for patients in England and Wales who were enrolled in the STAMPEDE trial.

The investigators were able to obtain data on clinical fracture incidence for 2145 (72%) of the overall 2962 patients enrolled in STAMPEDE. There were 796 patients with no metastases (M0) and 1349 patients with metastases (M1).

Jones explained that the researchers identified clinical fracture events “using a bespoke pre-specified coding framework of International Classification of Diseases (ICD 10) diagnosis and Classification of Interventions and Procedures (OPCS 4) procedure codes.”

The researchers used Multivariate Cox regression models to determine the specific effect of zoledronic on fracture risk, adjusting for age, N stage, WHO performance status, Gleason score, and NSAID use.

Across all patients, the 5-year incidence of fracture was 6.4%. The rate was significantly higher in patients with metastatic disease, at 9.6% vs 2.1% in patients with non-metastatic disease (P <.0001). Additionally, in the population with metastatic disease, the 5-year fracture incidence was lower in patients who received zoledronic acid at 4.55% vs 12.9%, respectively (P <.0001).

Discussing the implications of his research for clinical practice, Jones said, “Currently, zoledronic acid is not routinely advocated in the castration-sensitive setting. But these data support that it does, in fact, reduce fracture risk…So the results raise the question, ‘Should we be offering bone protection routinely to these men who are starting long-term ADT?’”

References

1. Jones C, Sachdeva A, Murphy L, et al. Clinical fracture incidence in metastatic hormone-sensitive prostate cancer (mHSPC) and risk-reduction following addition of zoledronic acid to androgen deprivation therapy (ADT) with or without docetaxel (DOC): long-term results from 2 phase 3 trials from the STAMPEDE platform protocol. Presented at 2023 AUA Annual Meeting. April 27-May 1, 2023; Chicago, IL. Abstract MP11-13.

2. James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163-1177. doi:10.1016/S0140-6736(15)01037-5