Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial

Saad, Fred; Carles, Joan; Gillessen, Silke; Heidenreich, Axel; Heinrich, Daniel; Gratt, Jeremy; Lévy, Jérémy; Miller, Kurt; Nilsson, Sten; Petrenciuc, Oana; Tucci, Marco; Wirth, Manfred; Federhofer, Judith; O’Sullivan, Joe M.

doi:10.1016/s1470-2045(16)30173-5

Cited by 266 publications

(232 citation statements)

References 24 publications

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“…Elevated alkaline phosphatase and low hemoglobin levels are recognized poor prognostic factors for survival. 7,10 It might be expected that poor prognosis patients would be less likely to respond or complete therapy; however other poor prognostic factors, like LDH and performance status, were not different between the two patient groups.…”

Section: Discussionmentioning

confidence: 99%

“…These cut points were selected a priori based on median values for hemoglobin in our population, and on previous reports of association with cycle completion for ALP. 9,10 Median OS was ascertained for the entire cohort, and compared between groups completing 5 vs. <5 cycles using log rank test. Patients that were lost to followup were censored with the assumption of non-informative censoring.…”

Section: Study Analysismentioning

confidence: 99%

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A population-based study of the use of radium 223 in metastatic castration-resistant prostate cancer: Factors associated with treatment completion

Parimi

Tsang

Alexander

et al. 2017

CUAJ

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Introduction: Radium 223 (Ra223) given for six cycles has proven efficacy in clinical trials, but its population-level generalizability has not been well-described. The objectives of this study were to describe population-based Ra223 use in the abiraterone and enzalutamide era and identify factors associated with completion. Methods: All Ra223 patients at the British Columbia Cancer Agency between September 2013 and February 2016 were identified. Patients who completed <5 vs. ≥5 cycles were compared on patient characteristics, lines of prior therapy, prostate-specific antigen (PSA) and alkaline phosphatase (ALP) decline >30% from baseline (R30%), and survival, to identify factors associated with therapy completion. Results: Ninety-one patients were identified; 48 (52.7%) completed >5 cycles. Median overall survival (mOS) was 10.7 months, PSA and ALP R30% were 21% and 52%, respectively. Completion of <5 cycles was associated with higher baseline ALP (p=0.05) and lower baseline hemoglobin (Hb) levels (p=0.03). Patients in the ≥5 cycles group had longer mOS than those in the <5 cycles group (16.2 vs. 5.9 months; p<0.0001), as well as higher PSA R30% (33.3% vs. 7.0%; p=0.002) and ALP R30% (66.7% vs. 34.9%; p=0.03). Patients with ALP ≥220 and Hb ≤118 had 3.85 times the odds of not completing ≥5 cycles vs. ALP <220 and Hb >118. Conclusions: Compared to clinical trials, patients in a populationbased setting had more lines of therapy and shorter survival. Lower ALP and higher hemoglobin were associated with completion of >5 cycles, longer mOS, and greater incidence of PSA and ALP response.

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Section: Discussionmentioning

confidence: 99%

Section: Study Analysismentioning

confidence: 99%

A population-based study of the use of radium 223 in metastatic castration-resistant prostate cancer: Factors associated with treatment completion

Parimi

Tsang

Alexander

et al. 2017

CUAJ

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“…A recent single-arm phase IIIb international early access program (iEAP) reported no new safety concerns for radium-223 when administered to patients with mCRPC and symptomatic or asymptomatic bone metastases in routine clinical practice. 31,32 In subgroup analyses of this study, radium-223 appeared to be more effective and was equally well-tolerated when given concomitantly with abiraterone and/or enzalutamide. 31 It has also been shown that radium-223 can be safely combined with bone-supportive agents including denosumab and bisphosphonates, and external beam radiation therapy.…”

Section: Clinical Developmentmentioning

confidence: 68%

The Contemporary Use of Radium-223 in Metastatic Castration-resistant Prostate Cancer

Heinrich

Bektic

Bergman

et al. 2018

Clinical Genitourinary Cancer

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Radium-223 dichloride (radium-223) was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases in the United States and Europe in 2013. This followed a reported overall survival benefit for patients treated with radium-223 and best standard of care (BSoC) when compared with placebo and BSoC in the ALpharadin in SYMptomatic Prostate CAncer (ALSYMPCA) trial. At that time, docetaxel was the standard first-line choice for patients with metastatic CRPC (mCRPC). Since then, the treatment landscape has changed dramatically with new hormonal agents (abiraterone and enzalutamide) considered to be the first-line choice for many patients. The optimal patient profile for radium-223 in the modern setting, and its best use either in sequence or in combination with other approved agents are unclear, with few definitive guidelines available. This article reports on the views of a group of urologists and medical oncologists experienced in treating patients with mCRPC with radium-223 in routine clinical practice. The aim is to provide an overview of the current use of radium-223 in the treatment of patients with mCRPC, and to discuss best practices for patient selection and on-treatment monitoring. Where agreement was reached, guidance on the optimal use of radium-223 is provided.

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“…The median OS was higher in these patients than in those who did not receive these agents, in addition, the association of denosumab with 223 Ra improved OS (5).…”

Section: Association Sequence and Interactionsmentioning

confidence: 79%

“…Such resistance to castration occurs in most patients (2) and, despite the approval of new therapeutic agents, mCRPCa remains a lethal disease (3). Nowadays the new therapeutic landscape for patients affected by mCRPCa aims to extend overall survival (OS) and includes cytotoxic, new-generation anti-androgens, immunotherapeutics and radiopharmaceuticals (4,5).…”

Section: Abstract 223 Ra Prolongs Overall Survival In Symptomatic Pamentioning

confidence: 99%

Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

Buroni

Persico

Pasi

et al. 2016

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Abstract. 223 Prostate cancer (PCa) is the most common malignancy in men (1). In patients affected by advanced PCa, defined as hormonesensitive disease since the tumor still requires androgen for growth, androgen deprivation therapy (ADT), including luteinizing hormone-releasing hormone (LHRH) agonists, antagonists and anti-androgens, represents the first-line treatment. Unfortunately some cancer cells develop resistance to ADT, indicating the progression of the disease to metastatic castration-resistant prostate cancer (mCRPCa). Such resistance to castration occurs in most patients (2) and, despite the approval of new therapeutic agents, mCRPCa remains a lethal disease (3). Nowadays the new therapeutic landscape for patients affected by mCRPCa aims to extend overall survival (OS) and includes cytotoxic, new-generation anti-androgens, immunotherapeutics and radiopharmaceuticals (4, 5).Bones are the preferred site of metastasis. Almost 90% of men who die from PCa have bone-metastatic disease (6), with a 5-year OS rate of 20%. Due to the fragility of bone with metastases, with the related risk of pain, fractures, spinal cord compression and hematological consequences, several drugs have been developed to treat the osseous involvement of this disease. In previous years, the optimal treatment aimed to relieve pain and reduce skeletal morbidity.Besides systemic therapies, bone-targeted agents that focus their activity on bone, such as bisphosphonates, monoclonal antibody and radiopharmaceuticals, have become available. The bisphosphonate zoledronic acid, the antibody to receptor activator of nuclear factor kappa-B ligand (RANKL) denosumab and radiopharmaceuticals [such as 89 Sr and 153 Sm-ethylene diamine tetramethylene phosphonate ( 153 Sm-EDTMP)], were approved for delaying skeletal-related events (SREs) and for the palliation of bone pain from mCRPCa. Radionuclide TherapyRadionuclide therapy is known to deliver ionizing radiation to tumor sites, thereby killing cancer cells (7). Bone-targeted radiopharmaceuticals localize their radiation to sites of high bone remodeling. 5719

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Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial

Cited by 266 publications

References 24 publications

A population-based study of the use of radium 223 in metastatic castration-resistant prostate cancer: Factors associated with treatment completion

A population-based study of the use of radium 223 in metastatic castration-resistant prostate cancer: Factors associated with treatment completion

The Contemporary Use of Radium-223 in Metastatic Castration-resistant Prostate Cancer

Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

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