Bone-Protecting Agents in mCRPC
An expert discusses how the PEACE III trial demonstrated that combining radium-223 with enzalutamide significantly improved radiographic progression-free survival and overall survival compared with enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC) who had bone metastases and limited prior treatment exposure.
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Bone-protective agents represent a critical component of mCRPC treatment protocols, as demonstrated by the mandatory use of these agents in the PEACE III trial. Standard of care includes monthly administration of zoledronic acid or denosumab for patients with mCRPC, typically continued for several years before potentially spacing treatments. These agents significantly reduce the risk of skeletal-related events (SREs), which include spinal cord compression, pathological fractures, and the need for surgical intervention or radiation therapy to bone metastases.
The importance of bone protection became evident through the ERA 223 trial, which studied radium-223 plus abiraterone vs abiraterone alone. This earlier study revealed concerning rates of SREs, particularly fractures, predominantly in patients not receiving bone health agents. Subsequent analysis confirmed that patients treated with bone-protective agents experienced substantially lower rates of complications, leading to the mandatory bone protection requirement in PEACE III.
The PEACE III trial results validated this approach, showing significantly reduced and acceptably low rates of SREs when bone-protective agents were mandated. This finding reinforces the critical importance of incorporating bone health agents into treatment regimens, particularly when using combination therapies involving radium-223 and other cancer-directed treatments. The SREs can be severely debilitating, limiting patient independence and causing significant pain, making their prevention through bone-protective agents essential for maintaining quality of life and treatment tolerability in patients with mCRPC.
