Interim analysis of the REASSURE (Radium-223 alpha Emitter Agent in non-intervention Safety Study in mCRPC popUlation for long-teRm Evaluation) study

patient characteristics and safety according to prior use of chemotherapy in routine clinical practice

Sabina Dizdarevic, Peter Meidahl Petersen, Markus Essler, Annibale Versari, Jean Cyril Bourre, Christian la Fougère, Riccardo Valdagni, Giovanni Paganelli, Samer Ezziddin, Ján Kalinovský, Inga Bayh, Yong Du

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose: REASSURE is a global, prospective, non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Here we report an interim analysis of patients according to previous use of chemotherapy. Methods: Radium-223 was administered in routine clinical practice. Interim safety analysis was planned after enrolment of the first 600 patients. Patient characteristics and safety data by previous administration of chemotherapy (docetaxel and/or cabazitaxel) were investigated. Results: This interim analysis included 583 patients. Median duration of observation was 7 months (range, 0–20). Nineteen patients treated with concomitant chemotherapy were excluded, 564 (97%) were eligible for exploratory analysis according to prior use of chemotherapy; 190 (34%) had previously received and completed chemotherapy, and 374 (66%) had not. In the prior versus no prior chemotherapy group, a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 (22% vs 11%) and > 20 metastatic lesions (26% vs 15%), median alkaline phosphatase (162.0 vs 115.0 U/L) and prostate-specific antigen (132.0 vs 40.2 ng/mL) levels were higher, and a lower proportion completed 6 radium-223 injections (45% vs 63%). Drug-related treatment-emergent adverse events (TEAEs) occurred in 63 and 48%, and haematological drug-related TEAEs in 21 and 9% of patients who had or had not previously received chemotherapy. Four drug-related deaths were reported, all in the prior chemotherapy group. Conclusions: The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies, irrespective of prior chemotherapy use. Haematological TEAEs occurred more frequently in the prior chemotherapy group, presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy. Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline, and a lower proportion discontinued radium-223 treatment.

Original languageEnglish
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Radium
Patient Safety
Safety
Drug Therapy
Population
docetaxel
Pharmaceutical Preparations
Therapeutics
Castration
Prostate-Specific Antigen
Alkaline Phosphatase
Prostatic Neoplasms
Bone Marrow
Observation

Keywords

  • Cabazitaxel
  • Current practice
  • Docetaxel
  • Metastatic prostate cancer
  • Radium-223
  • Treatment sequence

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{b3b7110145ce4e9694ea6e17643f2ca4,
title = "Interim analysis of the REASSURE (Radium-223 alpha Emitter Agent in non-intervention Safety Study in mCRPC popUlation for long-teRm Evaluation) study: patient characteristics and safety according to prior use of chemotherapy in routine clinical practice",
abstract = "Purpose: REASSURE is a global, prospective, non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Here we report an interim analysis of patients according to previous use of chemotherapy. Methods: Radium-223 was administered in routine clinical practice. Interim safety analysis was planned after enrolment of the first 600 patients. Patient characteristics and safety data by previous administration of chemotherapy (docetaxel and/or cabazitaxel) were investigated. Results: This interim analysis included 583 patients. Median duration of observation was 7 months (range, 0–20). Nineteen patients treated with concomitant chemotherapy were excluded, 564 (97{\%}) were eligible for exploratory analysis according to prior use of chemotherapy; 190 (34{\%}) had previously received and completed chemotherapy, and 374 (66{\%}) had not. In the prior versus no prior chemotherapy group, a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 (22{\%} vs 11{\%}) and > 20 metastatic lesions (26{\%} vs 15{\%}), median alkaline phosphatase (162.0 vs 115.0 U/L) and prostate-specific antigen (132.0 vs 40.2 ng/mL) levels were higher, and a lower proportion completed 6 radium-223 injections (45{\%} vs 63{\%}). Drug-related treatment-emergent adverse events (TEAEs) occurred in 63 and 48{\%}, and haematological drug-related TEAEs in 21 and 9{\%} of patients who had or had not previously received chemotherapy. Four drug-related deaths were reported, all in the prior chemotherapy group. Conclusions: The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies, irrespective of prior chemotherapy use. Haematological TEAEs occurred more frequently in the prior chemotherapy group, presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy. Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline, and a lower proportion discontinued radium-223 treatment.",
keywords = "Cabazitaxel, Current practice, Docetaxel, Metastatic prostate cancer, Radium-223, Treatment sequence",
author = "Sabina Dizdarevic and Petersen, {Peter Meidahl} and Markus Essler and Annibale Versari and Bourre, {Jean Cyril} and {la Foug{\`e}re}, Christian and Riccardo Valdagni and Giovanni Paganelli and Samer Ezziddin and J{\'a}n Kalinovsk{\'y} and Inga Bayh and Yong Du",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00259-019-4261-y",
language = "English",
journal = "European Journal of Pediatrics",
issn = "0340-6199",
publisher = "Springer Berlin Heidelberg",

}

TY - JOUR

T1 - Interim analysis of the REASSURE (Radium-223 alpha Emitter Agent in non-intervention Safety Study in mCRPC popUlation for long-teRm Evaluation) study

T2 - patient characteristics and safety according to prior use of chemotherapy in routine clinical practice

AU - Dizdarevic, Sabina

AU - Petersen, Peter Meidahl

AU - Essler, Markus

AU - Versari, Annibale

AU - Bourre, Jean Cyril

AU - la Fougère, Christian

AU - Valdagni, Riccardo

AU - Paganelli, Giovanni

AU - Ezziddin, Samer

AU - Kalinovský, Ján

AU - Bayh, Inga

AU - Du, Yong

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: REASSURE is a global, prospective, non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Here we report an interim analysis of patients according to previous use of chemotherapy. Methods: Radium-223 was administered in routine clinical practice. Interim safety analysis was planned after enrolment of the first 600 patients. Patient characteristics and safety data by previous administration of chemotherapy (docetaxel and/or cabazitaxel) were investigated. Results: This interim analysis included 583 patients. Median duration of observation was 7 months (range, 0–20). Nineteen patients treated with concomitant chemotherapy were excluded, 564 (97%) were eligible for exploratory analysis according to prior use of chemotherapy; 190 (34%) had previously received and completed chemotherapy, and 374 (66%) had not. In the prior versus no prior chemotherapy group, a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 (22% vs 11%) and > 20 metastatic lesions (26% vs 15%), median alkaline phosphatase (162.0 vs 115.0 U/L) and prostate-specific antigen (132.0 vs 40.2 ng/mL) levels were higher, and a lower proportion completed 6 radium-223 injections (45% vs 63%). Drug-related treatment-emergent adverse events (TEAEs) occurred in 63 and 48%, and haematological drug-related TEAEs in 21 and 9% of patients who had or had not previously received chemotherapy. Four drug-related deaths were reported, all in the prior chemotherapy group. Conclusions: The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies, irrespective of prior chemotherapy use. Haematological TEAEs occurred more frequently in the prior chemotherapy group, presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy. Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline, and a lower proportion discontinued radium-223 treatment.

AB - Purpose: REASSURE is a global, prospective, non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Here we report an interim analysis of patients according to previous use of chemotherapy. Methods: Radium-223 was administered in routine clinical practice. Interim safety analysis was planned after enrolment of the first 600 patients. Patient characteristics and safety data by previous administration of chemotherapy (docetaxel and/or cabazitaxel) were investigated. Results: This interim analysis included 583 patients. Median duration of observation was 7 months (range, 0–20). Nineteen patients treated with concomitant chemotherapy were excluded, 564 (97%) were eligible for exploratory analysis according to prior use of chemotherapy; 190 (34%) had previously received and completed chemotherapy, and 374 (66%) had not. In the prior versus no prior chemotherapy group, a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 (22% vs 11%) and > 20 metastatic lesions (26% vs 15%), median alkaline phosphatase (162.0 vs 115.0 U/L) and prostate-specific antigen (132.0 vs 40.2 ng/mL) levels were higher, and a lower proportion completed 6 radium-223 injections (45% vs 63%). Drug-related treatment-emergent adverse events (TEAEs) occurred in 63 and 48%, and haematological drug-related TEAEs in 21 and 9% of patients who had or had not previously received chemotherapy. Four drug-related deaths were reported, all in the prior chemotherapy group. Conclusions: The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies, irrespective of prior chemotherapy use. Haematological TEAEs occurred more frequently in the prior chemotherapy group, presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy. Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline, and a lower proportion discontinued radium-223 treatment.

KW - Cabazitaxel

KW - Current practice

KW - Docetaxel

KW - Metastatic prostate cancer

KW - Radium-223

KW - Treatment sequence

UR - http://www.scopus.com/inward/record.url?scp=85060061291&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060061291&partnerID=8YFLogxK

U2 - 10.1007/s00259-019-4261-y

DO - 10.1007/s00259-019-4261-y

M3 - Article

JO - European Journal of Pediatrics

JF - European Journal of Pediatrics

SN - 0340-6199

ER -