Abstract
Background:
Radium-223 is approved by the US Food and Drug Administration and European Medicines Agency for the treatment of metastatic castration-resistant prostate cancer (mCRPC). There are currently no markers for selecting patients most likely to complete radium-223 treatment.
Patients and Methods:
In this phase IIIb, international, single-arm study, patients received radium-223, 55 kBq/kg, every 4 weeks for ≤6 cycles. Primary end points were safety and overall survival. In post hoc analyses patients were grouped according to number of radium-223 injections received (1-4 or 5-6). Associations between baseline covariates and number of injections were investigated.
Results:
Of 696 eligible patients, 473 (68%) had received 5 to 6 radium-223 injections and 223 (32%) 1 to 4 injections. Patients with less pain (moderate-severe vs. none-mild, odds ratio [OR], 0.41; P < .0001), lower Eastern Cooperative Oncology Group performance status (≥2 vs. 0-1, OR, 0.51; P = .0074), lower prostate-specific antigen level (>141 μg/L vs. ≤141 μg/L, OR, 0.40; P < .0001), and higher hemoglobin level (<10 g/dL vs. ≥10 g/dL, OR, 0.50; P = .0206) were more likely to receive 5 to 6 than 1 to 4 injections. Median overall survival was not reached and was 6.3 months (95% confidence interval, 5.4-7.4) in patients who had received 5 to 6 and 1 to 4 radium-223 injections, respectively. Adverse events were less common in patients who received 5 to 6 than 1 to 4 injections; anemia was reported in 87 (18%) and 64 (29%) patients, respectively.
Conclusion:
Patients with less advanced mCRPC are more likely to receive 5 to 6 radium-223 injections and to achieve better overall survival. Consideration of baseline and disease characteristics is recommended before initiation of radium-223 treatment.
Radium-223 is approved by the US Food and Drug Administration and European Medicines Agency for the treatment of metastatic castration-resistant prostate cancer (mCRPC). There are currently no markers for selecting patients most likely to complete radium-223 treatment.
Patients and Methods:
In this phase IIIb, international, single-arm study, patients received radium-223, 55 kBq/kg, every 4 weeks for ≤6 cycles. Primary end points were safety and overall survival. In post hoc analyses patients were grouped according to number of radium-223 injections received (1-4 or 5-6). Associations between baseline covariates and number of injections were investigated.
Results:
Of 696 eligible patients, 473 (68%) had received 5 to 6 radium-223 injections and 223 (32%) 1 to 4 injections. Patients with less pain (moderate-severe vs. none-mild, odds ratio [OR], 0.41; P < .0001), lower Eastern Cooperative Oncology Group performance status (≥2 vs. 0-1, OR, 0.51; P = .0074), lower prostate-specific antigen level (>141 μg/L vs. ≤141 μg/L, OR, 0.40; P < .0001), and higher hemoglobin level (<10 g/dL vs. ≥10 g/dL, OR, 0.50; P = .0206) were more likely to receive 5 to 6 than 1 to 4 injections. Median overall survival was not reached and was 6.3 months (95% confidence interval, 5.4-7.4) in patients who had received 5 to 6 and 1 to 4 radium-223 injections, respectively. Adverse events were less common in patients who received 5 to 6 than 1 to 4 injections; anemia was reported in 87 (18%) and 64 (29%) patients, respectively.
Conclusion:
Patients with less advanced mCRPC are more likely to receive 5 to 6 radium-223 injections and to achieve better overall survival. Consideration of baseline and disease characteristics is recommended before initiation of radium-223 treatment.
| Original language | English |
|---|---|
| Pages (from-to) | 348-355. |
| Journal | Clinical genitourinary cancer |
| Volume | 17 |
| Issue number | 5 |
| Early online date | 31 May 2019 |
| DOIs | |
| Publication status | Published - 01 Oct 2019 |
Bibliographical note
Funding Information:This study was sponsored by Bayer . The iEAP study was funded by Bayer . The funder was responsible for the study design, data management and statistical analysis. Data interpretation was performed in collaboration with the study steering committee and the authors. The funder supported development of the manuscript through provision of medical writing assistance. Professor Saad had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors had the final responsibility for the decision to submit for publication. Dr Paul Hoban of Cancer Communications and Consultancy Ltd provided medical writing assistance, which was funded by Bayer .
Funding Information:
Professor Saad has a compensated consultancy role with, and has received research funding from, Bayer, Astellas, Janssen and Sanofi; Professor Gillessen has compensated consultancy and advisory roles with AAA International, Active Biotech AB IDMC, Astellas Pharma, Bayer, Bristol-Myers Squibb, Clovis, Curevac, Dendron Corporation, Ferring, Innocrin Pharmaceuticals, Janssen-Cilag, MaxiVAX SA, Millennium, Pharmaceuticals, Novartis, Orion, Pfizer, Roche, and Sanofi Aventis, and has participated in Speakers Bureaus (compensated) for Janssen and Novartis, and has a patent application for a biomarker method (WO 2009138392 A1); Dr Heinrich has received honoraria from Janssen-Cilag, Astellas, and Bayer, has compensated consultancy/advisory roles with Astellas, Bayer, and Amgen, and has had travel/accommodation expenses reimbursed from Bayer; Dr Keizman has received honoraria from and has compensated consultancy and advisory roles with Pfizer, Sanofi, Bayer, and Novartis, and has had travel/accommodation/expenses reimbursed from Pfizer and Bayer; Professor O'Sullivan has participated in advisory boards and speaker's bureaus for Bayer, Janssen, and Sanofi, and has received research funding (institute) from Bayer; Professor Nilsson has received honoraria from Bayer, Astellas, Ipsen, Sanofi-Genzyme, Novartis, Roche, and Janssen for advisory board participation and lectures; Professor Miller has received honoraria from Bayer, Janssen, and Amgen, and has compensated consultancy/advisory roles with Astellas, Astra Zeneca, Bristol-Myers Squibb, Ferring, Janssen, MSD, Novartis, Roche, and Sotio; Professor Wirth has compensated consultancy or advisory roles with ABX, Apogepha, Astellas, Amgen, Janssen-Cilag, Bayer, and MSD, and has provided expert testimony for ABX; Drs Reeves and Seger are salaried employees of Bayer; Dr Carles has a compensated consultancy role and has participated in scientific advisory boards for Johnson & Johnson, Astellas, Bayer, Amgen, Pfizer, and BMS, and has participated in speaker's bureaus for Bayer and Johnson & Johnson; Professor Heidenreich has received honoraria from Amgen, Astellas, Bayer, Dendreon, Ferring, Ipsen, Janssen, Pfizer, Sanofi, and Takeda, and has received research funding from Amgen, Astellas, and Sanofi.This study was sponsored by Bayer. The iEAP study was funded by Bayer. The funder was responsible for the study design, data management and statistical analysis. Data interpretation was performed in collaboration with the study steering committee and the authors. The funder supported development of the manuscript through provision of medical writing assistance. Professor Saad had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors had the final responsibility for the decision to submit for publication. Dr Paul Hoban of Cancer Communications and Consultancy Ltd provided medical writing assistance, which was funded by Bayer.
Publisher Copyright:
© 2019 The Authors
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
Keywords
- Baseline characteristics
- Bone metastases
- Injections
- Targeted alpha therapy
- Treatment completion
ASJC Scopus subject areas
- Oncology
- Urology
Access to Document
- Disease Characteristics and Completion of Treatment in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Radium-223 in an International Early Access Program
Copyright 2019 the authors. Published by Elsevier Inc. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.