Dr Jones on Clinical Fracture Incidence in mHSPC

Craig Jones, MBChB, urology SPR, Christie and Salford Royal NHS Foundation Trust, discusses findings from an analysis of fracture incidence in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase 2/3 STAMPEDE trial (NCT00268476) platform protocol.

Dr Jones on the Effects of Zoledronic Acid on Fracture Risk in mHSPC

STAMPEDE randomized patients with HSPC to receive androgen deprivation therapy (ADT) alone, ADT plus docetaxel, ADT plus zoledronic acid, or ADT plus docetaxel and zoledronic acid. An analysis of routinely collected data from this trial aimed to quantify fracture incidence in patients with metastatic and nonmetastatic disease and evaluate the effects of zoledronic acid on fracture risk.

In patients with nonmetastatic disease, the 5-year fracture incidence was 2.1% vs 9.6% in those with metastatic disease. Additionally, when patients with metastatic disease were stratified by zoledronic acid treatment status, the 5-year fracture incidence was 4.5% in those who received ADT plus docetaxel and zoledronic acid vs 12.9% in those who received ADT plus docetaxel. This separation of the fracture incidence curves translated to a 64% fracture risk reduction with zoledronic acid in the population with mHSPC.

Dr Jones on Fracture Risk Awareness and Reduction in mHSPC

These data indicate the importance of monitoring bone health in patients with mHSPC, Jones says. The high fracture incidence in patients with metastatic disease supports the routine use of bisphosphonates like zoledronic acid to decrease fracture risk, Jones explains.

Optimal zoledronic acid dosing remains an unanswered question regarding these findings, Jones notes. In STAMPEDE, patients received zoledronic acid at 4 mg every 3 weeks for 6 cycles and then every 4 weeks for 2 years. This is an intense dose for patients to receive indefinitely and may contribute to an increased incidence of adverse effects such as osteonecrosis of the jaw, Jones emphasizes. However, the high fracture incidence rate with ADT and docetaxel alone signifies the need for bone protection in all patients with mHSPC, and longer follow-up may demonstrate the potential role for zoledronic acid in patients with nonmetastatic disease as well, Jones concludes.