Prevention of Skeletal Events in the Therapy of Patients with Advanced Prostate Cancer
Prostate cancer most commonly forms metastases in the bones. In patients with this advanced disease, skeletal events occur, negatively affecting their quality of life. Zoledronic acid and denosumab are used to prevent their occurrence, and their results in this indication were evaluated and compared in the cited study below.
Complications Associated with Bone Metastases
Patients with metastatic prostate cancer most commonly suffer from bone metastases (relative incidence of bone metastases is 65−75%). Bone metastases often lead to complications such as pain, spinal cord compression, and fractures − collectively, these complications are referred to as skeletal-related events (SREs). They cause loss of mobility, social engagement, and reduced quality of life. The treatment of bone metastases in men with prostate cancer is palliative, aiming to control the disease to extend life, reduce pain, and increase mobility.
Currently, the treatment of metastatic prostate cancer includes androgen deprivation therapy. However, almost all patients progress to metastatic castration-resistant prostate cancer (mCRPC). New therapies targeting bone cells directly for patients with mCRPC (abiraterone, enzalutamide, and radium-223) are also being introduced. Bone-targeted antiresorptive agents, such as zoledronic acid and denosumab, are used to prevent SREs.
Comparison of Denosumab and Zoledronic Acid
Zoledronic acid inhibits osteoclasts and thus bone resorption. It has been shown to reduce the incidence of SREs in patients with prostate cancer with bone metastases. Denosumab is a human monoclonal antibody that inhibits the differentiation and maturation of osteoclasts.
Results from a clinical study including 1901 patients with mCRPC showed that administration of 120 mg of denosumab every 4 weeks significantly prolonged the time to the first SRE in the study by 3.6 months compared to 4 mg of zoledronic acid every 4 weeks. The median time to the first SRE (pathological fracture, radiation therapy to the bone, bone surgery, or spinal cord compression) in the study was 20.7 months for denosumab and 17.1 months for zoledronic acid (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.71–0.95; p = 0.008). A significantly lower number of SREs was observed in the denosumab group compared to the zoledronic acid group (difference of 90 SREs). Denosumab also reduced the incidence of first and subsequent SREs by 18% compared to zoledronic acid (rate ratio [RR] 0.82; 95% CI 0.71–0.94; p = 0.008).
Denosumab also delayed the onset of moderate/severe pain by 1.8 months (6.5 vs. 4.7 months; p < 0.001) and the need for pain relief by 2.6 months (10.3 vs. 7.7 months; p < 0.001) compared to zoledronic acid.
The safety profile of denosumab and zoledronic acid therapy was similar. A higher incidence of acute phase reaction was observed with zoledronic acid (20.2 vs. 8.7%), while hypocalcemia was more frequent with denosumab (9.6 vs. 5%). However, denosumab did not affect renal function and did not require dose adjustment compared to zoledronic acid.
Conclusion
The goal of palliative therapy for mCRPC is the prevention of SREs that result from bone metastases. The results indicate that denosumab is superior to zoledronic acid in preventing SREs, leading to a longer period without SREs and an overall lower number of SREs in patients with mCRPC with bone metastases.
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Source: Leung A. K. Optimizing skeletal-related events prevention in patients with advanced prostate cancer. Asia Pac J Clin Oncol 2020; 16 (Suppl. 3): 4−6, doi: 10.1111/ajco.13315.
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