Dataset Information

Ra-223 Treatment for Bone Metastases in Castrate-Resistant Prostate Cancer: Practical Management Issues for Patient Selection.

ABSTRACT: Bone metastases are common in men with metastatic castrate-resistant prostate cancer (mCRPC), occurring in 30% of patients within 2 years of castrate resistance and in >90% of patients over the disease course. There are 6 US Food and Drug Administration-approved therapies for mCRPC with demonstrated survival benefit. Of these, only radium-223 (Ra-223) specifically targets bone metastases, delays development of skeletal-related events, and improves survival. This review discusses key data from the ALSYMPCA trial, which contributed to the approval of Ra-223. Data from other trials are highlighted to provide further insight into which patients might benefit from Ra-223. Special patient populations are described, as well as other considerations for the administration of Ra-223. Finally, ongoing trials of Ra-223 combined with other therapies for mCRPC are discussed. These include combining Ra-223 with sipuleucel-T or immunooncology agents, to enhance immune responses, and trials in mildly symptomatic or asymptomatic patients. To date, the optimal timing, sequence, and combinations of Ra-223 with other agents are yet to be determined. The goals of this review are to provide insight into practical aspects of patient selection for Ra-223 treatment and to discuss key therapeutic strategies using the 6 approved mCRPC agents in patients with bone metastases. Results from ongoing trials should help guide the practitioner in using Ra-223 in patients with mCRPC.

SUBMITTER: Den RB

PROVIDER: S-EPMC6445613 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ra-223 Treatment for Bone Metastases in Castrate-Resistant Prostate Cancer: Practical Management Issues for Patient Selection.

Den Robert B RB George Daniel D Pieczonka Christopher C McNamara Megan M

American journal of clinical oncology 20190401 4

Bone metastases are common in men with metastatic castrate-resistant prostate cancer (mCRPC), occurring in 30% of patients within 2 years of castrate resistance and in >90% of patients over the disease course. There are 6 US Food and Drug Administration-approved therapies for mCRPC with demonstrated survival benefit. Of these, only radium-223 (Ra-223) specifically targets bone metastases, delays development of skeletal-related events, and improves survival. This review discusses key data from th ...[more]

PMID: 30844849

Similar Datasets

Project description:BACKGROUND:Radiation therapy with radium-223 dichloride improves overall survival, reduces symptomatic skeletal events in Caucasian patients with castration-resistant prostate cancer (CRPC) and bone metastases, and is well tolerated. We report here the results of the first efficacy and safety study of radium-223 dichloride in a Japanese population. METHODS:In this open-label, uncontrolled, non-randomized, phase I trial, radium-223 dichloride was given to Japanese patients with CRPC and ?2 bone metastases in 4-week cycles. The patients were divided into three cohorts, with cohort 1 and the expansion cohort receiving injections of radium-223 dichloride [55 kBq/kg body weight (BW)] every 4 weeks (Q4W) for up to six injections, and cohort 2 receiving an initial single radium-223 dichloride injection of 110 kBq/kg BW followed by up to five injections of 55 kBq/kg BW Q4W. Safety was determined via adverse event (AE) reporting, and biochemical bone markers were assessed for treatment efficacy. RESULTS:In total 19 patients received at least one dose of radium-223 dichloride and 18 patients experienced at least one treatment-emergent AE (TEAE) of which the most common were anemia, thrombocytopenia, and lymphocytopenia. Serious AEs were reported in three patients but none were drug-related. In the patients of cohort 1 + expansion cohort (55 kBq/kg BW Q4W treatment; n = 16), prostate-specific antigen levels remained stable or slightly increased while the bone alkaline phosphatase (ALP) level significantly decreased. The response rates of bone ALP (?30 and ?50% reductions) were 81.8 and 36.4% at week 12, and 81.3 and 50.0% at the end of treatment. CONCLUSIONS:Radium-223 dichloride was well tolerated in these Japanese patients and, at a dose of 55 kBq/kg BW, efficacy on biomarkers was as expected. The outcomes in Japanese patients were consistent with those reported in other non-Japanese populations. TRIAL REGISTRATION:ClinicalTrials.gov record NCT01565746.

Project description:BackgroundRadium-223, a targeted alpha therapy, is used to treat symptomatic patients with castration-resistant prostate cancer (CRPC) and bone metastases. Data for radium-223 in asymptomatic CRPC patients with bone metastases are lacking.MethodsThis was a prospective, single-arm phase 3b study. Patients with metastatic CRPC (malignant lymphadenopathy not exceeding 6 cm was allowed, visceral disease was excluded) received radium-223, 55 kBq/kg intravenously, every 4 weeks for up to 6 cycles. Co-primary endpoints were safety and overall survival. Post hoc analyses were performed according to baseline asymptomatic or symptomatic disease status. Asymptomatic status was defined as no pain and no opioid use at baseline.ResultsSeven hundred eight patients received ≥1 radium-223 injection: 548 (77%) were symptomatic to various degrees, and 135 (19%) were asymptomatic. Asymptomatic patients had more favorable baseline disease characteristics than symptomatic. A lower proportion of asymptomatic versus symptomatic patients had received prior abiraterone (25% vs 35%) and prior docetaxel (52% vs 62%). A higher proportion of asymptomatic (71%) versus symptomatic (55%) patients completed radium-223 treatment. Overall survival (hazard ratio [HR] 0.486), time to disease progression (HR 0.722) and time to first symptomatic skeletal event (HR 0.328) were better in asymptomatic than symptomatic patients. Alkaline phosphatase (ALP) response rates were similar (46% vs 47%), and ALP normalization (44% vs 25%) and prostate-specific antigen response rates (21% vs 13%) were higher in asymptomatic than symptomatic patients. A lower proportion of asymptomatic patients reported treatment-emergent adverse events (TEAEs, 61% vs 79%), grade 3-4 TEAEs (29% vs 40%) and drug-related TEAEs (28% vs 44%). There were two treatment-related deaths, both in patients with baseline symptomatic disease.ConclusionsUsing radium-223 earlier in the disease course, when patients are asymptomatic or minimally symptomatic, may enable patients to complete treatment and optimize treatment outcome compared to symptomatic patients, and therefore may allow sequencing with other life-prolonging therapies.Trial registrationThe study was registered with ClinicalTrials.gov , number NCT01618370 on June 13, 2012 and the European Union Clinical Trials Register, EudraCT number 2012-000075-16 on April 4, 2012.

Dataset Information

Ra-223 Treatment for Bone Metastases in Castrate-Resistant Prostate Cancer: Practical Management Issues for Patient Selection.

Publications

Ra-223 Treatment for Bone Metastases in Castrate-Resistant Prostate Cancer: Practical Management Issues for Patient Selection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets