Effects of Denosumab versus Zoledronic Acid in Patients with Castration-Resistant Prostate Cancer and Bone Metastases

2012 ◽  
Vol 08 (02) ◽  
pp. 94 ◽  
Author(s):  
Neal Shore ◽  
Carsten Goessl ◽  
◽  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Human Monoclonal Antibody ◽  
Bone Destruction ◽  
Comprehensive Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Efficacy Analysis ◽  
Castration Resistant ◽  
Skeletal Complications

Progression of castration-resistant prostate cancer often leads to bone metastases, increasing the risk of skeletal-related events (SREs). The use of antiresorptive therapies such as denosumab, a human monoclonal antibody and zoledronic acid (ZA), a bisphosphonate, reduces bone destruction by inhibiting osteoclast function and survival. In 2002, ZA was approved for the prevention of skeletal complications in patients with bone disease from myeloma or bone metastases from solid tumors including prostate cancer. Recently, efficacy analysis demonstrated superiority of denosumab to ZA for the prevention or delay of SREs in 1,901 patients with prostate cancer and bone metastases, significantly delaying the time to first SRE and time to first and subsequent SRE compared to ZA. Decreases in bone turnover markers were greater with denosumab, mirroring the reduction in SREs. The reported incidence of adverse events were similar between denosumab and ZA. Advanced prostate cancer patients require long-term disease management where maintenance of overall bone health is an essential component of a comprehensive treatment program.

A randomized phase III trial of denosumab versus zoledronic acid in patients with bone metastases from castration-resistant prostate cancer.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA4507-LBA4507 ◽  
Author(s):  
K. Fizazi ◽  
M. A. Carducci ◽  
M. R. Smith ◽  
R. Damião ◽  
J. E. Brown ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cancer Progression ◽  
Controlled Trial ◽  
Human Monoclonal Antibody ◽  
Bone Destruction ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

LBA4507 Background: Bone metastases from hormone-refractory (castration-resistant) prostate cancer (CRPC) are associated with RANKL-mediated osteoclast activation resulting in bone destruction and skeletal-related events (SRE). Denosumab is a fully human monoclonal antibody against RANKL. This phase III, randomized, double-blind, active-controlled trial compared the efficacy and safety of denosumab vs. zoledronic acid (ZA) in patients with metastatic CRPC. Methods: Patients (n = 1,901) with CRPC and at least 1 bone metastasis, but no prior IV bisphosphonate use, received either SC denosumab 120 mg and IV placebo (n = 950), or SC placebo and IV ZA 4 mg (n = 951) adjusted for creatinine clearance every 4 weeks. All patients were instructed to take supplemental calcium and vitamin D. The primary endpoint was time to first on-study SRE, defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression. Results: Denosumab significantly delayed the time to first on-study SRE compared with ZA, (HR 0.82 ; 95% CI: 0.71, 0.95 ; p = 0.008.) The median time to first on-study SRE was 20.7 mo denosumab vs. 17.1 mo ZA, a difference of 3.6 months. Denosumab also significantly delayed the time to first and subsequent on-study SRE (multiple event analysis) (HR 0.82 ; 95% CI: 0.71, 0.94 ; p = 0.004). Greater suppression of the bone turnover markers uNTx and BSAP occurred in denosumab patients compared with ZA (p < 0.0001 for both). Overall, adverse event (AE) rates (97% each) and serious AEs (63% denosumab, 60% ZA) were similar, irrespective of potential relationship to study drugs. AEs of hypocalcemia were reported in 13% and 6% of denosumab and ZA patients. Osteonecrosis of the jaw occurred in 22 (2.3%) denosumab compared with 12 (1.3%) ZA patients (p = 0.09). Overall survival (HR 1.03 ; 95% CI: 0.91, 1.17 ; p = 0.65) and time to cancer progression (HR 1.06; 95% CI: 0.95, 1.18; p = 0.30) were similar between treatment arms. Conclusions: Denosumab demonstrated superiority over ZA in delaying or preventing SREs in patients with bone metastases from CRPC. Adverse events were consistent in both treatment groups with those previously reported in advanced cancer populations. [Table: see text]

Bone modifying agents in veterans with castration-resistant prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6582-6582
Author(s):  
Jordan Bauman ◽  
Kyle Kumbier ◽  
Jennifer A. Burns ◽  
Jordan Sparks ◽  
Phoebe A. Tsao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Specific Antigen ◽  
Veterans Health ◽  
Health Administration ◽  
Castration Resistant Prostate Cancer ◽  
National Guidelines ◽  
Castration Resistant ◽  
Unit Increase

6582 Background: Skeletal related events (SREs) are a known complication for the 80% of men with metastatic prostate cancer who have bone metastases. Previous studies have demonstrated that bone modifying agents (BMAs) such as zoledronic acid and denosumab reduce SREs in men with metastatic castration-resistant prostate cancer who have bone metastases and are now recommended by national guidelines. We sought to investigate factors associated with use of BMAs in Veterans with CRPC across the Veterans Health Administration (VA). Methods: Using the VA Corporate Data Warehouse, consisting of aggregated medical record data from 130 facilities, we used an algorithm previously published to identify men with a diagnosis of castration-resistant prostate cancer (CRPC) based on rising prostate specific antigen (PSA) levels while on androgen deprivation therapy and who received systemic treatment for CRPC with one of the commonly used therapies: abiraterone, enzalutamide, docetaxel, ketoconazole between 2010 and 2017. To account for clustering among facilities, we used a multilevel multivariable logistic regression to determine the association of patient and disease-specific variables on the odds of a patient receiving a BMA after they started treatment for CRPC. Results: Of 4,998 patients with CRPC in our cohort, 2223 (44%) received either zoledronic acid or denosumab at some point after they were initiated on treatment for CRPC. After adjusting for other variables and accounting for a facility, the odds of receiving a BMA decreased by 3% for every additional year of age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.96-0.98), and decreased significantly with increasing comorbid conditions (OR 0.94, 95% CI 0.72-0.98 for Charlson Comorbidity Index [CCI] of 1; OR 0.69, 95% CI 0.59-0.81 for CCI 2+). Patients who were Black had 25% lower odds of receiving a BMA than patients who were White (OR 0.75, 95% CI 0.65-0.87). PSA at time of CRPC treatment start had a small but not significant effect on receipt of a BMA (OR 1.04, 95% CI 1.00-1.08) for every unit increase of PSA on the log scale. PSA doubling time was not associated with receipt of a BMA. The presence of a diagnosis code for bone metastases was far lower than expected in this cohort of patients with CRPC (40.7%), and thus was not included in the model. We did not expect the presence of bone metastases to vary significantly among the other independent variables. Conclusions: Despite most patients with CRPC historically having bone metastases, less than half of patients with CRPC received a BMA. Patients who are older, had more comorbidities, or were Black were less likely to receive a BMA after starting treatment for CRPC. Understanding factors that lead to different patterns of treatment can guide initiatives toward more guideline-concordant care.

scholarly journals Randomized Controlled Trial of Early Zoledronic Acid in Men With Castration-Sensitive Prostate Cancer and Bone Metastases: Results of CALGB 90202 (Alliance)

2014 ◽  
Vol 32 (11) ◽  
pp. 1143-1150 ◽  
Author(s):  
Matthew R. Smith ◽  
Susan Halabi ◽  
Charles J. Ryan ◽  
Arif Hussain ◽  
Nicholas Vogelzang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Controlled Trial ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Primary Analysis ◽  
Open Label ◽  
Castration Resistant

Purpose Zoledronic acid decreases the risk for skeletal-related events (SREs) in men with castration-resistant prostate cancer and bone metastases but its role earlier in the natural history of the disease is unknown. This phase III study evaluated the efficacy and safety of earlier treatment with zoledronic acid in men with castration-sensitive metastatic prostate cancer. Patients and Methods Men with castration-sensitive prostate cancer and bone metastases whose androgen-deprivation therapy was initiated within 6 months of study entry were randomly assigned in a blinded 1:1 ratio to receive zoledronic acid (4 mg intravenously every 4 weeks) or a placebo. After their disease progressed to castration-resistant status, all patients received open-label treatment with zoledronic acid. The primary end point was time to first SRE, defined as radiation to bone, clinical fracture, spinal cord compression, surgery to bone, or death as a result of prostate cancer. Target accrual was 680 patients. Primary analysis was planned after 470 SREs. The study was discontinued prematurely (645 patients; 299 SREs) after the corporate supporter withdrew study drug supply. Results Early zoledronic acid was not associated with increased time to first SRE. The median time to first SRE was 31.9 months in the zoledronic acid group (95% CI, 24.2 to 40.3) and 29.8 months in the placebo group (95% CI, 25.3 to 37.2; hazard ratio, 0.97; 95% CI, 0 to 1.17; one-sided stratified log-rank P = .39). Overall survival was similar between the groups (hazard ratio, 0.88; 95% CI, 0.70 to 1.12; P = .29). Rates of adverse events were similar between the groups. Conclusion In men with castration-sensitive prostate cancer and bone metastases, early treatment with zoledronic acid was not associated with lower risk for SREs.

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