KEY TAKEAWAYS
- Two phase 3 trials evaluated long-term fracture events in mHSPC pts following the addition of ZA with ADT ± Doc.
- Pts were randomly assigned in 2:1 between different treatment arms: ADT, ADT+ZA, ADT+Doc, and ADT+Doc+ZA.
- The long-term results confirm that bone protective agents can reduce clinically significant fractures in mHSPC.
The study evaluated the long-term treatment toxicity and clinical efficacy of zoledronic acid (ZA) as a bone protective agent in metastatic hormone-sensitive prostate cancer (mHSPC). Researchers analyzed HES data up to 2018 for patients (pts) randomized 2:1 between different treatment arms. Arm A received androgen deprivation therapy (ADT), Arm B received ADT+ZA, Arm C received ADT+docetaxel (Doc), and Arm E received ADT+Doc+ZA. ZA was administered for six 3-weekly cycles, followed by 4-weekly cycles for 2 years. Clinical fracture events were identified using a pre-specified coding framework of the International Classification of Diseases (ICD 10) diagnosis and Classification of Interventions and Procedures (OPCS 4) procedure codes. Multivariate Cox regression models were used to adjust for age, N stage, WHO performance status, Gleason score, and NSAID and assess the impact of ZA on fracture risk.
Based on the data, out of 2,962 patients, 2,145 were eligible (796 M0 and 1,349 M1), making up 72% of the total. The 5-year incidence of fractures was 6.4%, with M1 patients having a higher incidence (9.6% in M1 vs 2.1% in M0, p<0.0001). However, the incidence was lower in M1 patients who were administered ZA (4.55% with ZA vs 12.9% without ZA, p<0.0001). The use of ZA reduced the risk of fractures in M1 patients (HR 0.36, 95% CI 0.22-0.57, p<0.0005), while it did not have the same effect on M0 patients (HR 0.67, 95% CI 0.32-1.39, p=0.28).
RCHD analysis shows a high fracture rate in M1 patients in the STAMPEDE study. Allocation of ZA with ADT±Doc can significantly reduce fractures in mHSPC patients. These findings highlight the critical role of bone protective agents in reducing the incidence of clinically significant fractures in patients with mHSPC.
Source: https://www.auajournals.org/doi/10.1097/JU.0000000000003226.13
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT00268476
Jones, Craig; Sachdeva, Ashwin; Murphy, Laura; Murray, Macey; Brown, Louise; McCloskey, Eugene; Brown, Janet; Attard, Gerhardt; Parmar, Mahesh; James, Nicholas; Sydes, Matthew; Clarke, Noel MP11-13 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, Journal of Urology: April 2023 – Volume 209 – Issue Supplement 4
doi: 10.1097/JU.0000000000003226.13
