Dataset Information

Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation.

ABSTRACT: Radium-223 dichloride ([223Ra]RaCl2; Ra-223) is a targeted alpha-emitting radiopharmaceutical which results in an overall survival and health related quality of life (HRQoL) benefit in symptomatic patients with metastatic castration resistant prostate cancer (mCRPC) and predominantly bone metastasis. Although effective, options to select patients who will derive treatment benefit and to monitor and predict treatment outcomes are limited. PSA response and radiographic evaluation are commonly used in mCRPC treatment assessment but are not informative in Ra-223 treated patients. Consequently, there is a clear need for predictive and prognostic tools. In this review, we discuss the physiology of bone metastases and the mechanism of action and efficacy of Ra-223 treatment, as well as offering an outline of current innovative prognostic and predictive biomarkers.

SUBMITTER: van der Zande K

PROVIDER: S-EPMC8431634 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation.

van der Zande Kim K Oyen Wim J G WJG Zwart Wilbert W Bergman Andries M AM

Cancers 20210827 17

Radium-223 dichloride ([<sup>223</sup>Ra]RaCl<sub>2</sub>; Ra-223) is a targeted alpha-emitting radiopharmaceutical which results in an overall survival and health related quality of life (HRQoL) benefit in symptomatic patients with metastatic castration resistant prostate cancer (mCRPC) and predominantly bone metastasis. Although effective, options to select patients who will derive treatment benefit and to monitor and predict treatment outcomes are limited. PSA response and radiographic evalua ...[more]

PMID: 34503156

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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

Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation.

Publications

Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation.

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