Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
Radium-223, CRPC, Phase IV, Safety study
Brief summary
Observational study in the routine clinical practice setting to evaluate the short and long term safety profile of Radium-223 in metastatic castration resistant prostate cancer patients and to evaluate the risk of developing second primary cancers.
Interventions
DRUGRadium-223 dichloride (Xofigo, BAY88-8223)
This is a non-interventional study, the drug is used in its authorized indication from commercial supply. The decision to treat with Radium-223 will be agreed upon between the physician and the patient independently and prior to providing the patient study information. Treatment with Radium-223 should follow the approved local product information.
Sponsors
Bayer
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Treatment decision to Radium-223 needs to be made independent from and before patient enrollment in the study * Histologically or cytologically confirmed castration resistant adenocarcinoma of the prostate with bone metastases * Signed informed consent
Exclusion criteria
* Previously treated with Radium-223 for any reason * Currently treated in clinical trials including other Radium-223 studies * Planned for the systemic concomitant use of other radiopharmaceuticals for treatment of prostate cancer or for other use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Marrow Suppression: Number of Participants Who Underwent Subsequent Chemotherapy That Experienced Febrile Neutropenia or Hemorrhage | From first dose of subsequent chemotherapy up to 6 months (up to 183 days) after the last administration of chemotherapy | Participants who receive subsequent cytotoxic chemotherapy were followed for the development of febrile neutropenia and hemorrhage up to 6 months after the last administration of chemotherapy at a frequency based on local clinical practice. |
| Number of Participants With Drug-related Treatment-emergent Adverse Events | From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 30 days after the last administration of Radium-223 | Treatment-emergent was defined as any event arising or worsening on the day of or after start of radium-223 until 30 days after last injection. |
| Number of Participants With Drug-related SAEs | From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks), up to 7 years after the last dose of Radium-223 | All drug-related SAEs were collected up to 7 years after the last administration of radium-223. |
| Number of Participants With Therapeutic or Preventive Treatments for Bone Marrow Suppression | From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 6 months after last dose of Radium-223 | Bone marrow suppression relevant treatments for participants with subsequent chemotherapy (e.g., blood transfusion/erythropoietin/colony growth stimulating factors) |
| Incidences of Post-Radium-223 Treatment CTCAE Grade 3/4 Hematological Toxicities Based on Bone Marrow Suppression | From last Radium-223 dose up to 6 months post last dose of Radium-223 | Hematological toxicities were summarized by the Common Terminology Criteria for Adverse Events (CTCAE) coding system and the worst grade. The grading system ranges from Grade 1 (mild) to Grade 5 (death). The percentage of participants with post-radium-223 treatment CTCAE grade 3 or 4 hematological toxicities that occurred within 183 days from last radium-223 injection are reported |
| Bone Marrow Suppression: Number of Participants With Abnormal Platelet Count or White Blood Cell Count (WBC) | From 30 days after last dose of Radium-223 up to 6 months after last dose | Participants with a platelet count or WBC less than the lower limit of normal at 6 months post last dose of Radium- 223 |
| Number of Participants With Second Primary Malignancies (SPM) | From the initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 7 years after the last dose of Radium-223 | Second primary malignancies (SPMs) are defined as new malignancies unrelated to prostate cancer or progression of prostate cancer. All types of SPMs will be collected irrespectively of their relationship to Radium-223. All reported SPMs will be summarized as assessed by the physician |
| Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 30 days after the last administration of Radium-223 | Treatment-emergent was defined as any event arising or worsening on the day of or after start of radium-223 until 30 days after last injection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Worst Pain Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 6 months after the last dose of Radium-223 | The Brief pain inventory short form (BPI-SF) questionnaire was used to assess pain severity on a scale from 0 (no pain) to 10 (worst pain). The BPI-SF questionnaire was requested prior to each injection of Radium-223 and also used at each follow-up visit until 6 months after the last injection of Radium-223. The pain severity score was calculated per visit. Completion of the BPI-SF questionnaire by the patient was voluntary. Since this is an observational study, the treatment regimen may not necessarily follow the recommended schedule of one cycle every 4 weeks for all participants |
| The Pain Interference Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | From initiation of Radium-223 (treatment period up to 6 months which includes 4 cycles every 4 weeks) up to 6 months after the last dose of Radium-223 | The Brief pain inventory short form (BPI-SF) questionnaire was used to assess pain interference on a scale from 0 (does not interfere) to 10 (completely interferes). The BPI-SF questionnaire was requested prior to each injection of Radium-223 and also used at each follow-up visit until 6 months after the last injection of Radium-223. The pain interference score was calculated per visit. Completion of the BPI-SF questionnaire by the patient was voluntary Since this is an observational study, the treatment regimen may not necessarily follow the recommended schedule of one cycle every 4 weeks for all participants |
| Percentage of Participants With Bone Fractures | From initiation of Radium-223 (treatment period up to 6 months which includes 6 cyles every 4 weeks) up to 7 years post last dose of Radium-223 | Bone fractures were identified by MedDRA HLGTs: Fractures: HLGT = Fractures. |
| Percentage of Participants With Bone Associated Events | From initiation of Radium-223 (treatment period up to 6 months which includes 6 cyles every 4 weeks) up to 7 years post last dose of Radium-223 | Bone associated events were identified by MedDRA HLGTs: Bone associated events: HLGT = Bone disorders (excl congenital and fractures) |
| Overall Survival | From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 7 years after the last dose of Radium-223 | Overall survival was defined as the time interval from the start of Radium-223 therapy to death due to any cause. Patients whose death was not confirmed at the time of data-cut were censored at the last date known to be alive. |
Countries
Argentina, Austria, Belgium, Canada, Colombia, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Luxembourg, Mexico, Netherlands, Portugal, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 188 treatment centers in 20 countries from 20 August 2014 (first patient first visit) to 02 August 2024 (last patient last visit)
Pre-assignment details
Overall, 1567 participants were screened and a total of 1472 participants started treatment with Radium-223
Participants by arm
| Arm | Count |
|---|---|
| Radium-223 Participants with castration-resistant prostate cancer (CRPC) with bone metastases have received Radium-223 as part of their routine care at participating study centers | 1,472 |
| Total | 1,472 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1,308 |
| Overall Study | Lost to Follow-up | 84 |
| Overall Study | Patients without documented end of observation due to premature site closure | 5 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 52 |
Baseline characteristics
| Characteristic | Radium-223 |
|---|---|
| Age, Continuous | 73.0 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 170 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1159 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 143 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 16 Participants |
| Race/Ethnicity, Customized Black or African American | 63 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants |
| Race/Ethnicity, Customized Not reported | 95 Participants |
| Race/Ethnicity, Customized White | 1295 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1472 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1,308 / 1,472 |
| other Total, other adverse events | 837 / 1,472 |
| serious Total, serious adverse events | 325 / 1,472 |
Outcome results
Primary
Bone Marrow Suppression: Number of Participants Who Underwent Subsequent Chemotherapy That Experienced Febrile Neutropenia or Hemorrhage
Participants who receive subsequent cytotoxic chemotherapy were followed for the development of febrile neutropenia and hemorrhage up to 6 months after the last administration of chemotherapy at a frequency based on local clinical practice.
Time frame: From first dose of subsequent chemotherapy up to 6 months (up to 183 days) after the last administration of chemotherapy
Population: Safety analysis set (SAF)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radium-223 | Bone Marrow Suppression: Number of Participants Who Underwent Subsequent Chemotherapy That Experienced Febrile Neutropenia or Hemorrhage | 23 Participants |
Primary
Bone Marrow Suppression: Number of Participants With Abnormal Platelet Count or White Blood Cell Count (WBC)
Participants with a platelet count or WBC less than the lower limit of normal at 6 months post last dose of Radium- 223
Time frame: From 30 days after last dose of Radium-223 up to 6 months after last dose
Population: Safety analysis set (SAF)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Radium-223 | Bone Marrow Suppression: Number of Participants With Abnormal Platelet Count or White Blood Cell Count (WBC) | Abnormal platelet count (<50x10^9/L) | No | 398 Participants |
| Radium-223 | Bone Marrow Suppression: Number of Participants With Abnormal Platelet Count or White Blood Cell Count (WBC) | Abnormal platelet count (<50x10^9/L) | Yes | 49 Participants |
| Radium-223 | Bone Marrow Suppression: Number of Participants With Abnormal Platelet Count or White Blood Cell Count (WBC) | Abnormal platelet count (<50x10^9/L) | Missing | 1025 Participants |
| Radium-223 | Bone Marrow Suppression: Number of Participants With Abnormal Platelet Count or White Blood Cell Count (WBC) | Abnormal neutrophil count (<1x10^9/L) | No | 247 Participants |
| Radium-223 | Bone Marrow Suppression: Number of Participants With Abnormal Platelet Count or White Blood Cell Count (WBC) | Abnormal neutrophil count (<1x10^9/L) | Yes | 6 Participants |
| Radium-223 | Bone Marrow Suppression: Number of Participants With Abnormal Platelet Count or White Blood Cell Count (WBC) | Abnormal neutrophil count (<1x10^9/L) | Missing | 1219 Participants |
Primary
Incidences of Post-Radium-223 Treatment CTCAE Grade 3/4 Hematological Toxicities Based on Bone Marrow Suppression
Hematological toxicities were summarized by the Common Terminology Criteria for Adverse Events (CTCAE) coding system and the worst grade. The grading system ranges from Grade 1 (mild) to Grade 5 (death). The percentage of participants with post-radium-223 treatment CTCAE grade 3 or 4 hematological toxicities that occurred within 183 days from last radium-223 injection are reported
Time frame: From last Radium-223 dose up to 6 months post last dose of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radium-223 | Incidences of Post-Radium-223 Treatment CTCAE Grade 3/4 Hematological Toxicities Based on Bone Marrow Suppression | Grade 3 | 14.74 Percentage |
| Radium-223 | Incidences of Post-Radium-223 Treatment CTCAE Grade 3/4 Hematological Toxicities Based on Bone Marrow Suppression | Grade 4 | 1.77 Percentage |
| Radium-223 | Incidences of Post-Radium-223 Treatment CTCAE Grade 3/4 Hematological Toxicities Based on Bone Marrow Suppression | Total | 15.42 Percentage |
Primary
Number of Participants With Drug-related SAEs
All drug-related SAEs were collected up to 7 years after the last administration of radium-223.
Time frame: From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks), up to 7 years after the last dose of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radium-223 | Number of Participants With Drug-related SAEs | 88 Participants |
Primary
Number of Participants With Drug-related Treatment-emergent Adverse Events
Treatment-emergent was defined as any event arising or worsening on the day of or after start of radium-223 until 30 days after last injection.
Time frame: From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 30 days after the last administration of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radium-223 | Number of Participants With Drug-related Treatment-emergent Adverse Events | 537 Participants |
Primary
Number of Participants With Second Primary Malignancies (SPM)
Second primary malignancies (SPMs) are defined as new malignancies unrelated to prostate cancer or progression of prostate cancer. All types of SPMs will be collected irrespectively of their relationship to Radium-223. All reported SPMs will be summarized as assessed by the physician
Time frame: From the initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 7 years after the last dose of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radium-223 | Number of Participants With Second Primary Malignancies (SPM) | 24 Participants |
Primary
Number of Participants With Therapeutic or Preventive Treatments for Bone Marrow Suppression
Bone marrow suppression relevant treatments for participants with subsequent chemotherapy (e.g., blood transfusion/erythropoietin/colony growth stimulating factors)
Time frame: From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 6 months after last dose of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Radium-223 | Number of Participants With Therapeutic or Preventive Treatments for Bone Marrow Suppression | Patients with at least one of the bone marrow suppression relevant treatments | No | 1133 Participants |
| Radium-223 | Number of Participants With Therapeutic or Preventive Treatments for Bone Marrow Suppression | Patients with at least one of the bone marrow suppression relevant treatments | Yes | 339 Participants |
| Radium-223 | Number of Participants With Therapeutic or Preventive Treatments for Bone Marrow Suppression | Patients with any blood transfusions | No | 1155 Participants |
| Radium-223 | Number of Participants With Therapeutic or Preventive Treatments for Bone Marrow Suppression | Patients with any blood transfusions | Yes | 317 Participants |
| Radium-223 | Number of Participants With Therapeutic or Preventive Treatments for Bone Marrow Suppression | Patients receiving erythropoiesis stimulating drugs | No | 1448 Participants |
| Radium-223 | Number of Participants With Therapeutic or Preventive Treatments for Bone Marrow Suppression | Patients receiving erythropoiesis stimulating drugs | Yes | 24 Participants |
| Radium-223 | Number of Participants With Therapeutic or Preventive Treatments for Bone Marrow Suppression | Patients with colony stimulating factors | No | 1448 Participants |
| Radium-223 | Number of Participants With Therapeutic or Preventive Treatments for Bone Marrow Suppression | Patients with colony stimulating factors | Yes | 24 Participants |
Primary
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
Treatment-emergent was defined as any event arising or worsening on the day of or after start of radium-223 until 30 days after last injection.
Time frame: From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 30 days after the last administration of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radium-223 | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | 325 Participants |
Secondary
Overall Survival
Overall survival was defined as the time interval from the start of Radium-223 therapy to death due to any cause. Patients whose death was not confirmed at the time of data-cut were censored at the last date known to be alive.
Time frame: From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 7 years after the last dose of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radium-223 | Overall Survival | 15.6 Months |
Secondary
Percentage of Participants With Bone Associated Events
Bone associated events were identified by MedDRA HLGTs: Bone associated events: HLGT = Bone disorders (excl congenital and fractures)
Time frame: From initiation of Radium-223 (treatment period up to 6 months which includes 6 cyles every 4 weeks) up to 7 years post last dose of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 | Percentage of Participants With Bone Associated Events | 8.5 Percentage of participants |
Secondary
Percentage of Participants With Bone Fractures
Bone fractures were identified by MedDRA HLGTs: Fractures: HLGT = Fractures.
Time frame: From initiation of Radium-223 (treatment period up to 6 months which includes 6 cyles every 4 weeks) up to 7 years post last dose of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radium-223 | Percentage of Participants With Bone Fractures | 9.7 Percentage of participants |
Secondary
The Pain Interference Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire
The Brief pain inventory short form (BPI-SF) questionnaire was used to assess pain interference on a scale from 0 (does not interfere) to 10 (completely interferes). The BPI-SF questionnaire was requested prior to each injection of Radium-223 and also used at each follow-up visit until 6 months after the last injection of Radium-223. The pain interference score was calculated per visit. Completion of the BPI-SF questionnaire by the patient was voluntary Since this is an observational study, the treatment regimen may not necessarily follow the recommended schedule of one cycle every 4 weeks for all participants
Time frame: From initiation of Radium-223 (treatment period up to 6 months which includes 4 cycles every 4 weeks) up to 6 months after the last dose of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radium-223 | The Pain Interference Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Baseline/Treatment 1 | 3.283 Score | Standard Deviation 2.664 |
| Radium-223 | The Pain Interference Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Treatment cycle 2 (approximately at week 4) | 2.965 Score | Standard Deviation 2.588 |
| Radium-223 | The Pain Interference Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Treatment cycle 3 (approximately at week 8) | 2.656 Score | Standard Deviation 2.469 |
| Radium-223 | The Pain Interference Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Treatment cycle 5 (approximately at week 16) | 2.358 Score | Standard Deviation 2.408 |
| Radium-223 | The Pain Interference Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | First available follow-up measurement | 2.809 Score | Standard Deviation 2.57 |
| Radium-223 | The Pain Interference Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Treatment cycle 4 (approximately at week 12) | 2.587 Score | Standard Deviation 2.525 |
| Radium-223 | The Pain Interference Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Treatment cycle 6 (approximately at week 20) | 2.495 Score | Standard Deviation 2.425 |
| Radium-223 | The Pain Interference Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Last available follow-up measurement | 3.107 Score | Standard Deviation 2.774 |
Secondary
Worst Pain Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire
The Brief pain inventory short form (BPI-SF) questionnaire was used to assess pain severity on a scale from 0 (no pain) to 10 (worst pain). The BPI-SF questionnaire was requested prior to each injection of Radium-223 and also used at each follow-up visit until 6 months after the last injection of Radium-223. The pain severity score was calculated per visit. Completion of the BPI-SF questionnaire by the patient was voluntary. Since this is an observational study, the treatment regimen may not necessarily follow the recommended schedule of one cycle every 4 weeks for all participants
Time frame: From initiation of Radium-223 (treatment period up to 6 months which includes 6 cycles every 4 weeks) up to 6 months after the last dose of Radium-223
Population: Safety analysis set (SAF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radium-223 | Worst Pain Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Treatment cycle 2 (approximately at week 4) | 2.760 Score | Standard Deviation 2.251 |
| Radium-223 | Worst Pain Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Treatment cycle 3 (approximately at week 8) | 2.464 Score | Standard Deviation 2.222 |
| Radium-223 | Worst Pain Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Treatment cycle 5 (approximately at week 16) | 2.261 Score | Standard Deviation 2.223 |
| Radium-223 | Worst Pain Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Baseline/Treatment cycle 1 | 3.003 Score | Standard Deviation 2.189 |
| Radium-223 | Worst Pain Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Treatment cycle 4 (approximately at week 12) | 2.436 Score | Standard Deviation 2.309 |
| Radium-223 | Worst Pain Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Treatment cycle 6 (approximately at week 20) | 2.262 Score | Standard Deviation 2.21 |
| Radium-223 | Worst Pain Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | First available follow-up measurement | 2.458 Score | Standard Deviation 2.307 |
| Radium-223 | Worst Pain Score Over Time as Determined by Patient Responses on the Brief Pain Inventory Short Form (BPI-SF) Questionnaire | Last available follow-up measurement | 2.629 Score | Standard Deviation 2.424 |