Dataset Information

Radionuclide Therapies in Prostate Cancer: Integrating Radium-223 in the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer.

ABSTRACT: Metastatic castration-resistant prostate cancer (mCRPC) frequently metastasizes to the bone, often resulting in painful skeletal events, reduced quality of life, and reduced survival. The beta-emitting radiopharmaceuticals strontium-89 and samarium-153 alleviated pain in mCRPC patients with widespread skeletal metastases and have been associated with myelotoxicity. Radium-223, a first-in-class alpha-emitting radiopharmaceutical, prolonged overall survival, delayed symptomatic skeletal events, and improved quality of life, versus placebo, in patients with CRPC and symptomatic bone metastases and no visceral metastases. Radium-223 provided survival benefit to patients with CRPC and symptomatic bone metastases, regardless of prior docetaxel use. Importantly, prostate-specific antigen level and pain palliation were not a measure of radium-223 treatment response and should not alter the decision to administer all six radium-223 injections, the recommended regimen for survival benefit. Radium-223 was generally well tolerated, leading to ongoing clinical trials in combination with other therapeutics. Thus, radium-223 is a valuable addition to the mCRPC treatment armamentarium.

SUBMITTER: Nilsson S

PROVIDER: S-EPMC4715854 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Radionuclide Therapies in Prostate Cancer: Integrating Radium-223 in the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer.

Nilsson Sten S

Current oncology reports 20160201 2

Metastatic castration-resistant prostate cancer (mCRPC) frequently metastasizes to the bone, often resulting in painful skeletal events, reduced quality of life, and reduced survival. The beta-emitting radiopharmaceuticals strontium-89 and samarium-153 alleviated pain in mCRPC patients with widespread skeletal metastases and have been associated with myelotoxicity. Radium-223, a first-in-class alpha-emitting radiopharmaceutical, prolonged overall survival, delayed symptomatic skeletal events, an ...[more]

PMID: 26779616

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Project description:BackgroundThe treatment of metastatic castration-resistant prostate cancer has changed with the introduction of radium-223, cabazitaxel, abiraterone and enzalutamide. To assess value for money, their cost effectiveness in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel from the Dutch societal perspective was investigated.MethodsA cost-effectiveness analysis was conducted using efficacy, symptomatic skeletal-related event and safety data obtained from indirect treatment comparisons. Missing skeletal-related event data for cabazitaxel were conservatively assumed to be identical to radium-223. A Markov model combined these clinical inputs with Dutch-specific resource use and costs for metastatic castration-resistant prostate cancer treatment from a societal perspective. Total quality-adjusted life-years and costs in 2017 euros were calculated over a 5-year (lifetime) time horizon.ResultsRadium-223 resulted in €6092 and €4465 lower costs and 0.02 and 0.01 higher quality-adjusted life-years compared with abiraterone and cabazitaxel, respectively, demonstrating dominance of radium-223. Sensitivity analyses reveal a 64% (54%) chance of radium-223 being cost effective compared with abiraterone (cabazitaxel) at the informal €80,000 willingness-to-pay threshold. Compared with enzalutamide, radium-223 resulted in slightly lower quality-adjusted life-years (-0.06) and €7390 lower costs, revealing a 61% chance of radium-223 being cost effective compared with enzalutamide. The lower costs of radium-223 compared with abiraterone and enzalutamide are driven by lower drug costs and prevention of expensive skeletal-related events. Compared with cabazitaxel, the lower costs of radium-223 are driven by lower costs of the drug, administration and adverse events.ConclusionRadium-223 may be a less costly treatment strategy offering similar gains in health benefits compared with abiraterone, cabazitaxel and enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel from the Dutch societal perspective.

Project description:BackgroundRadium-223 is a targeted alpha-particle therapy that improves survival in men with metastatic castration resistant prostate cancer (mCRPC), particularly in men with elevated serum levels of bone alkaline phosphatase (B-ALP). We hypothesized that osteomimicry, a form of epithelial plasticity leading to an osteoblastic phenotype, may contribute to intralesional deposition of radium-223 and subsequent irradiation of the tumor microenvironment.MethodsWe conducted a pharmacodynamic study (NCT02204943) of radium-223 in men with bone mCRPC. Prior to and three and six months after radium-223 treatment initiation, we collected CTCs and metastatic biopsies for phenotypic characterization and CTC genomic analysis. The primary objective was to describe the impact of radium-223 on the prevalence of CTC B-ALP over time. We measured radium-223 decay products in tumor and surrounding normal bone during treatment. We validated genomic findings in a separate independent study of men with bone metastatic mCRPC (n = 45) and publicly accessible data of metastatic CRPC tissues.ResultsWe enrolled 20 men with symptomatic bone predominant mCRPC and treated with radium-223. We observed greater radium-223 radioactivity levels in metastatic bone tumor containing biopsies compared with adjacent normal bone. We found evidence of persistent Cellsearch CTCs and B-ALP (+) CTCs in the majority of men over time during radium-223 therapy despite serum B-ALP normalization. We identified genomic gains in osteoblast mimicry genes including gains of ALPL, osteopontin, SPARC, OB-cadherin and loss of RUNX2, and validated genomic alterations or increased expression at the DNA and RNA level in an independent cohort of 45 men with bone-metastatic CRPC and in 150 metastatic biopsies from men with mCRPC.ConclusionsOsteomimicry may contribute in part to the uptake of radium-223 within bone metastases and may thereby enhance the therapeutic benefit of this bone targeting radiotherapy.

Dataset Information

Radionuclide Therapies in Prostate Cancer: Integrating Radium-223 in the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer.

Publications

Radionuclide Therapies in Prostate Cancer: Integrating Radium-223 in the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer.

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