scholarly journals Practical update for the use of bone-targeted agents in patients with bone metastases from metastatic breast cancer or castration-resistant prostate cancer

2020 ◽  
Vol 27 (4) ◽  
Author(s):  
D. Southcott ◽  
A. Awan ◽  
K. Ghate ◽  
M. Clemons ◽  
R. Fernandes
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Metastatic Breast ◽  
Pathologic Fracture ◽  
Dose Schedule ◽  
Cord Compression ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Skeletal Related Events ◽  
Breast And Prostate Cancer

Bone metastases are a significant source of morbidity and mortality for patients with breast and prostate cancer. In this review, we discuss key practical themes regarding the use of bone-targeted agents (btas) such as bisphospho­nates and denosumab for managing bony metastatic disease. The btas both delay the onset and reduce the incidence of skeletal-related events (sres), defined as any or all of a need for radiation therapy or surgery to bone, pathologic fracture, spinal cord compression, or hypercalcemia of malignancy. They have more modest benefits for pain and other quality-of-life measures. Regardless of the benefits of btas, it should always be remembered that the palliative management of meta­static bone disease is multimodal and multidisciplinary. The collaboration of all disciplines is essential for optimal patient care. Special consideration is given to these key questions: What are btas, and what is their efficacy? What are their common toxicities? When should they be initiated? How do we choose the appropriate bta? What is the appropriate dose, schedule, and duration of btas?

scholarly journals Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2034
Author(s):  
Soraia Lobo-Martins ◽  
Arlindo R. Ferreira ◽  
André Mansinho ◽  
Sandra Casimiro ◽  
Kim Leitzel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Unmet Need ◽  
Bone Alkaline Phosphatase ◽  
Multicenter Clinical Trial ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Therapeutic Landscape ◽  
Skeletal Related Events ◽  
The Impact

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-related events (SREs) in patients with mCRPC. Less frequent BTA schedules are currently being studied to minimize adverse events. In this study, the impact of metastatic compartment (bone and extraskeletal metastases (BESM) vs. bone-only metastases (BOM)) on bone biomarker kinetics, time to first on-study SRE, and symptomatic skeletal events (SSEs) is evaluated. This is a retrospective analysis of the prospective, randomized, multicenter clinical trial of denosumab vs. zoledronic acid in patients with mCRPC and bone metastases. A total of 1901 patients were included, 1559 (82.0%) with BOM and 342 with BESM (18.0%). Bone metastases burden was balanced between groups. Baseline levels and normalization rates of corrected urinary N-terminal telopeptide and bone alkaline phosphatase did not differ between groups. However, BESM patients had a higher risk of SREs (adjusted HR 1.21; 95% CI 1.01–1.46; p = 0.043) and SSEs (adjusted HR 1.30; 95% CI 1.06–1.61; p = 0.014). This difference was more pronounced in the first 12 months of BTA treatment.In mCRPC, strategies of BTA schedule de-escalation may take into account presence of extraskeletal metastases.

Evaluation of prescribing practices of denosumab and zoledronic acid in breast and prostate cancer patients at University of Chicago Medicine.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24144-e24144
Author(s):  
Heng Yang ◽  
Randall W Knoebel ◽  
Sandeep Parsad ◽  
Emma Carroll ◽  
Walter Michael Stadler
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Metastatic Breast Cancer ◽  
Zoledronic Acid ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Adherence Rate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Breast And Prostate Cancer

e24144 Background: Zoledronic acid (ZA) and denosumab are both bone-modifying agents (BMAs) approved for use in patients with bone metastases with breast or prostate cancer as well as patients who are receiving aromatase inhibitors (breast cancer) or androgen deprivation therapy (prostate cancer). There are various frequencies of administration, doses, and duration of these agents depending on indication and extent of disease. Currently there is data to show that ZA can be given every 3 months in patients with metastatic breast and prostate cancer, however, there is no data that clearly indicates that denosumab every 3 months is non-inferior to every 28 days. This study aimed to analyze current prescribing patterns of ZA and denosumab in metastatic breast cancer and metastatic castration resistant prostate cancer patients at The University of Chicago Medicine (UCM). Methods: This was a retrospective study of 80 patients who received at least one dose of ZA or denosumab between July 1st 2018 to June 30th 2019 from UCM outpatient oncology clinic for the purpose of treating metastatic breast cancer or metastatic castration resistant prostate cancer in conjunction with standard antineoplastic therapy. All included patients must have bone metastases. Patients were divided into four groups by disease state (breast or prostate cancer) and BMA agent (ZA or denosumab). The primary outcome was BMA therapy adherence rate, which was defined by those who received greater than or equal to 80% of appropriately scheduled doses. Descriptive statistics were used for skeletal-related events (SREs) and BMA associated adverse effects. Results: Patients who received ZA achieved higher adherence rates (100% breast, 86% prostate) compared to patients that received denosumab (63% breast, 23% prostate). The most common reason for the lower adherence rate in denosumab groups was scheduling convenience. During the study period, there were 3, 0, 2 and 5 patients had SREs in the above four groups respectively. The predominant adverse event across all groups was hypocalcemia and two patients with prostate cancer on denosumab developed osteonecrosis of the jaw. The cost analysis showed using ZA as primary BMA agent might save up to 2.5 million dollars per year at UCM. Conclusions: The use ofZA was associated with higher adherence rates compared to denosumab. Implementing a pharmacy driven protocol for ZA use for patients with metastatic breast and prostate cancer may improve BMA regimen adherence rates and significantly reduce costs.

scholarly journals Bone-Targeted Therapies in Metastatic Castration-Resistant Prostate Cancer: Evolving Paradigms

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Joelle El-Amm ◽  
Ashley Freeman ◽  
Nihar Patel ◽  
Jeanny B. Aragon-Ching
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Kinase Inhibitors ◽  
Targeted Agents ◽  
Pain Palliation ◽  
Castration Resistant Prostate Cancer ◽  
Humanized Monoclonal Antibody ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Overall Survival Benefit

Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibiting RANK-L mediated bone resorption. While several radiopharmaceuticals were approved for pain palliation in mCRPC including strontium and samarium, alpharadin is the first radiopharmaceutical to show significant overall survival benefit. Contemporary therapeutic options including enzalutamide and abiraterone have effects on pain palliation and SREs as well. Other novel bone-targeted agents are currently in development, including the receptor tyrosine kinase inhibitors cabozantinib and dasatinib. Emerging therapeutics in mCRPC has resulted in great strides in preventing one of the most significant sources of complications of bone metastases.

Skeletal related events in patients with metastatic renal cell carcinoma: A retrospective review

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16118-e16118
Author(s):  
M. Secter ◽  
M. J. MacKenzie ◽  
P. O'Brien ◽  
F. Whiston
Keyword(s):  
Renal Cell Carcinoma ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Retrospective Review ◽  
Renal Cell ◽  
Length Of Hospital Stay ◽  
Pathologic Fracture ◽  
Cord Compression ◽  
Skeletal Related Events

e16118 Background: Approximately one third of patients with renal cell carcinoma (RCC) will develop bone metastases during the course of their disease. Previous studies suggest that the rate of skeletal related events (SREs) in patients with metastatic renal cell carcinoma is high, and that bisphosphonate therapy can lower the rate of SREs. We conducted a retrospective review of patients with metastatic renal cell carcinoma and bone metastases seen at our academic cancer centre. Methods: After approval by the Research Ethics Board, a retrospective review of all patients seen at the London Regional Cancer Centre with a diagnosis of RCC between January 2006 and December 2008 was performed. Data points collected included the number of patients with bone metastases, number of SREs, length of hospital stay, and treatments related to SREs. A SRE was defined as one of the following: pathologic fracture, spinal cord compression, radiotherapy or surgery to bone, or hypercalcemia in the presence of bone metastases. Results: 196 patients with metastatic RCC were identified. Of these, 63 (32%) had bone metastases. 75% of these patients with bone metastases received medical therapies including sunitinib, sorafenib or temsirolimus. 66% of patients received at least one dose of bisphosponate therapy. Common sites of metastases were vertebra (66%), pelvis (50%), and femur (42%). Of those with bone metastases, 61 (95%) experienced at least one SRE. 42% sustained a pathologic fracture; 28% suffered a spinal cord compression or cauda equina syndrome; 22% had surgery for bone metastases; 87.5% required radiotherapy and 27% had hypercalcemia. 40% of patients were hospitalized due to an SRE, and the mean length of hospital stay was 21 days (range 1–120 days). Conclusions: Despite significant recent improvements in the overall care of RCC, and expansion of the number of therapeutic options, bone metastases and consequent SREs continue to cause significant morbidity. These SREs come with frequent and prolonged hospitalizations. Our rate of SREs is actually higher than that documented in the placebo arm of a randomized trial of a bisphosphonate in RCC from the pre-tyrosine kinase era. Bone-related morbidity in mRCC remains a clinical problem with a significant unmet medical need. [Table: see text]

scholarly journals Cost-Effectiveness Analysis of 12-Versus 4-Weekly Administration of Bone-Targeted Agents in Patients with Bone Metastases from Breast and Castration-Resistant Prostate Cancer

2021 ◽  
Vol 28 (3) ◽  
pp. 1847-1856
Author(s):  
Megan M. Tu ◽  
Mark Clemons ◽  
Carol Stober ◽  
Ahwon Jeong ◽  
Lisa Vandermeer ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Bone Metastases ◽  
Group Versus ◽  
Metastatic Breast ◽  
Sensitivity Analyses ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Life Years ◽  
Weekly Group

A cost–utility analysis was performed based on the Rethinking Clinical Trials (REaCT) bone-targeted agents (BTA) clinical trial that compared 12-weekly (once every 12 weeks) (n = 130) versus 4-weekly (once every 4 weeks) (n = 133) BTA dosing for metastatic breast and castration-resistant prostate (CRPC) cancer. Using a decision tree model, we calculated treatment and symptomatic skeletal event (SSE) costs as well as quality-adjusted life-years (QALYs) for each treatment option. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of the study findings. The total cost of BTA treatment in Canadian dollars (C$) and estimated QALYs was C$8965.03 and 0.605 QALY in the 4-weekly group versus C$5669.95 and 0.612 QALY in the 12-weekly group, respectively. De-escalation from 4-weekly to 12-weekly BTA reduces cost (C$3293.75) and improves QALYs by 0.008 unit, suggesting that 12-weekly BTA dominates 4-weekly BTA in breast and CRPC patients with bone metastases. Sensitivity analysis suggests high levels of uncertainty in the cost-effectiveness findings. De-escalation of bone-targeted agents is cost-effective from the Canadian public payer’s perspective.

scholarly journals Bone Targeting Agents in Patients with Metastatic Prostate Cancer: State of the Art

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 546
Author(s):  
Veronica Mollica ◽  
Alessandro Rizzo ◽  
Matteo Rosellini ◽  
Andrea Marchetti ◽  
Angela Dalia Ricci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cord Compression ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Pathologic Fractures ◽  
Phase Iii Trials ◽  
Skeletal Related Events

Bone health represents a major issue in castration-resistant prostate cancer (CRPC) patients with bone metastases; in fact, the frequently prolonged use of hormonal agents causes important modifications in physiological bone turnover and most of these men will develop skeletal-related events (SREs), including spinal cord compression, pathologic fractures and need for surgery or radiation to bone, which are estimated to occur in almost half of this patient population. In the last decade, several novel therapeutic options have entered into clinical practice of bone metastatic CRPC, with recent approval of enzalutamide and abiraterone acetate, cabazitaxel chemotherapy and radium-223, on the basis of survival benefit suggested by landmark Phase III trials assessing these agents in this setting. Conversely, although bone-targeted agents (BTAs)—such as the bisphosphonate zoledronic acid and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab—are approved for the prevention of SREs, these compounds have not shown benefit in terms of overall survival. However, emerging evidence has suggested that the combination of BTAs and abiraterone acetate, enzalutamide and the radiopharmaceutical radium-223 could result in improved clinical outcomes and prolonged survival in bone metastatic CRPC. In this review, we will provide an overview on bone tropism of prostate cancer and on the role of BTAs in metastatic hormone-sensitive and castration-resistant prostate cancer.

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