PMID- 37251627
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230531
IS  - 2589-5370 (Electronic)
IS  - 2589-5370 (Linking)
VI  - 60
DP  - 2023 Jun
TI  - Clinical outcomes and treatment patterns in REASSURE: planned interim analysis of 
      a real-world observational study of radium-223 in metastatic castration-resistant 
      prostate cancer.
PG  - 101993
LID - 10.1016/j.eclinm.2023.101993 [doi]
LID - 101993
AB  - BACKGROUND: Radium-223, a targeted alpha therapy, is approved to treat 
      bone-dominant metastatic castration-resistant prostate cancer (mCRPC), based on 
      significantly prolonged overall survival versus placebo and a favourable safety 
      profile in the phase 3 ALSYMPCA study. ALSYMPCA was conducted when few other 
      treatment options were available, and prospectively collected data are limited on 
      the use of radium-223 in the current mCRPC treatment landscape. We sought to 
      understand long-term safety and treatment patterns in men who received radium-223 
      in real-world clinical practice. METHODS: REASSURE (NCT02141438) is a global, 
      prospective, observational study of radium-223 in men with mCRPC. Primary 
      outcomes are adverse events (AEs), including treatment-emergent serious AEs 
      (SAEs) and drug-related AEs during and </=30 days after radium-223 completion, 
      grade 3/4 haematological toxicities </=6 months after last radium-223 dose, 
      drug-related SAEs after radium-223 therapy completion, and second primary 
      malignancies. FINDINGS: Data collection commenced on Aug 20, 2014, and the data 
      cutoff date for this prespecified interim analysis was Mar 20, 2019 (median 
      follow-up 11.5 months [interquartile range 6.0-18.6]), 1465 patients were 
      evaluable. For second primary malignancies, 1470 patients were evaluable, 21 (1%) 
      of whom had a total of 23 events. During radium-223 therapy, 311 (21%) of 1465 
      patients had treatment-emergent SAEs, and 510 (35%) had drug-related AEs. In the 
      6 months after completion of radium-223 therapy, 214 (15%) patients had grade 3/4 
      haematological toxicities. Eighty patients (5%) had post-treatment drug-related 
      SAEs. Median overall survival was 15.6 months (95% confidence interval 14.6-16.5) 
      from radium-223 initiation. Patient-reported pain scores declined or stabilised. 
      Seventy (5%) patients had fractures. INTERPRETATION: REASSURE offers insight into 
      radium-223 use in global real-world clinical practice with currently available 
      therapies. At this interim analysis, with a median follow-up of almost 1 year, 1% 
      of patients had second primary malignancies, and safety and overall survival 
      findings were consistent with clinical trial experience. Final analysis of 
      REASSURE is due in 2024. FUNDING: Bayer HealthCare.
CI  - (c) 2023 Published by Elsevier Ltd.
FAU - Higano, Celestia S
AU  - Higano CS
AD  - Departments of Medicine and Urology, University of Washington, Fred Hutchinson 
      Cancer Research Center, Seattle, WA, USA.
FAU - George, Daniel J
AU  - George DJ
AD  - Departments of Medicine and Surgery, Duke Cancer Institute, Duke University, 
      Durham, NC, USA.
FAU - Shore, Neal D
AU  - Shore ND
AD  - Carolina Urologic Research Center, Myrtle Beach, SC, USA.
FAU - Sartor, Oliver
AU  - Sartor O
AD  - Departments of Medicine and Urology, Tulane Cancer Center, Tulane University 
      School of Medicine, New Orleans, LA, USA.
FAU - Miller, Kurt
AU  - Miller K
AD  - Department of Urology, Charite University Hospital, Berlin, Germany.
FAU - Conti, Peter S
AU  - Conti PS
AD  - Molecular Imaging Center, Keck School of Medicine of USC, Los Angeles, CA, USA.
FAU - Sternberg, Cora N
AU  - Sternberg CN
AD  - Englander Institute for Precision Medicine, Weill Cornell Department of Medicine, 
      Meyer Cancer Center, New York-Presbyterian Hospital, New York, NY, USA.
FAU - Saad, Fred
AU  - Saad F
AD  - Department of Urology, University of Montreal Hospital Center, Montreal, Quebec, 
      Canada.
FAU - Sade, Juan Pablo
AU  - Sade JP
AD  - Department of Clinical Oncology, Alexander Fleming Institute, Buenos Aires, 
      Argentina.
FAU - Bellmunt, Joaquim
AU  - Bellmunt J
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Smith, Matthew R
AU  - Smith MR
AD  - Genitourinary Oncology Program, Massachusetts General Hospital Cancer Center, 
      Boston, MA, USA.
FAU - Chandrawansa, Kumari
AU  - Chandrawansa K
AD  - Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
FAU - Sandstrom, Per
AU  - Sandstrom P
AD  - Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
FAU - Verholen, Frank
AU  - Verholen F
AD  - Bayer Consumer Care AG, Basel, Switzerland.
FAU - Tombal, Bertrand
AU  - Tombal B
AD  - Division of Urology, IREC, Cliniques Universitaires Saint Luc, UCLouvain, 
      Brussels, Belgium.
LA  - eng
PT  - Journal Article
DEP - 20230518
PL  - England
TA  - EClinicalMedicine
JT  - EClinicalMedicine
JID - 101733727
PMC - PMC10209672
OTO - NOTNLM
OT  - Clinical outcomes
OT  - Metastatic castration-resistant prostate cancer
OT  - Radium-223
COIS- All authors report support for the present manuscript from Bayer for medical 
      writing funding to Open Health. Celestia S. Higano reports support for the 
      present manuscript from Bayer for clinical trial funding to institution; grants 
      or contracts from AbbVie (Contract to develop unbranded educational slide set), 
      Vaccitech (Clinical trial consulting contract, no payments yet), and Verity; 
      consulting fees from the Prostate Cancer Clinical Trials Consortium (Consulting 
      PCCCTC medical monitor for trials sponsored by ESSA and Bayer), Prostate Cancer 
      Supportive Care Program (Consulting Medical Director), and Astellas, AstraZeneca, 
      Ferring, Genentech, Merck Sharp & Dohme, Myovant, Pfizer, Tolmar, and Vaccitech 
      (all advisory boards); payment or honoraria for lectures, presentations, speakers 
      bureaus, manuscript writing or educational events from Tolmar (medical writing); 
      payment for expert testimony from Ferring; participation on a Data Safety 
      Monitoring Board or Advisory Board for AstraZeneca, Exelixis, Advantagene/Candel, 
      and Alliance Foundation (all DSMBs). Daniel J. George reports grants or contracts 
      from Astellas, AstraZeneca, BMS, Calithera, Exelixis, J&J, Pfizer, Novartis, and 
      Sanofi (all paid to his institution); royalties or licenses from Up-to-Date (paid 
      to self); consulting fees from Bayer, Ideo Oncology, Merck, Michael J Hennessey, 
      Myovant, Propella, RevHealth, Seattle Genetics, WebMD, and Xcures (all paid to 
      self); payment or honoraria for lectures, presentations, speakers bureaus, 
      manuscript writing or educational events from Bayer, Exelixis, and Sanofi (all 
      paid to self); payment for expert testimony from Wilmer Hale (paid to self); 
      support for attending meetings and/or travel from Bayer, Exelixis, and Sanofi 
      (paid to self); participation on a Data Safety Monitoring Board or Advisory Board 
      for Janssen and AstraZeneca (both paid to self); and leadership or fiduciary role 
      in other board, society, committee or advocacy group, paid or unpaid, for AACR 
      (senior editor), Millennium Med Pub, and CAHO (Co-Editor-in-Chief) (all paid to 
      self). Neal D. Shore reports consulting fees from AbbVie, Alessa Therapeutics, 
      Akido, Arquer, Asieris, Astellas, Astra Zeneca, Bayer, BMS, Boston Scientific, 
      Clarity, Cold Genesys, Dendreon, Exact Images, Ferring, Foundation Medicine, 
      ImmunityBio, Incyte, Invitae, Janssen, Lantheus, Lilly, MDX, Merck, Minomic, 
      Myovant, Myriad, NGM, Nonagen, Novartis, NYMOX, Photocure, Pfizer, PlatformQ, 
      Profound, Promaxo, Protara, Sanofi, SesenBio, Speciality Networks, Telix, Tolmar, 
      Vaxiion; payment for expert testimony from Ferring. Oliver Sartor reports grants 
      or contracts from Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, 
      Constellation, Endocyte, Invitae, Janssen, Lantheus, Merck, Progenics, and 
      Tenebio; consulting fees from Advanced Accelerator Applications (AAA), Astellas, 
      AstraZeneca, Bayer, Blue Earth Diagnostics, Inc., Bavarian Nordic, Bristol Myers 
      Squibb, Clarity Pharmaceuticals, Clovis, Constellation, Dendreon, EMD Serono, 
      Fusion, Isotopen Technologien, Merck, Meunchen, Janssen, Myovant, Myriad, Noria 
      Therapeutics, Inc., NorthStar, Novartis, Noxopharm, Progenics, POINT Biopharma, 
      Pfizer, Sanofi, Tenebio, Telix, Theragnostics; payment or honoraria for lectures, 
      presentations, speakers bureaus, manuscript writing or educational events from 
      Advanced Accelerator Applications (AAA), Astellas, AstraZeneca, Bayer, Blue Earth 
      Diagnostics, Inc., Bavarian Nordic, Bristol Myers Squibb, Clarity 
      Pharmaceuticals, Clovis, Constellation, Dendreon, EMD Serono, Fusion, Isotopen 
      Technologien, Merck, Meunchen, Janssen, Myovant, Myriad, Noria Therapeutics, 
      Inc., NorthStar, Novartis, Noxopharm, Progenics, POINT Biopharma, Pfizer, Sanofi, 
      Tenebio, Telix, Theragnostics; patents planned, issued or pending: Koochekpour, 
      Sartor AO, inventors. Saposin C and receptors as targets for treatment of benign 
      and malignant disorders. US patent awarded January 23, 2007 (patent no. 
      7,166,691); participation on a Data Safety Monitoring Board or Advisory Board for 
      AstraZeneca, Jannsen, Pfizer, and Myovant; Leadership or fiduciary role in other 
      board, society, committee or advocacy group, paid or unpaid for Louisiana Cancer 
      Research Consortium - Board, LA. Cancer and Lung Trust; and stock or stock 
      options in Clarity Pharmaceuticals, Noria Therapeutics, Inc., Lilly, Clovis, 
      Glaxo Smith Kline, Abbvie, Cardinal Health, and United Health Group. Kurt Miller 
      reports consulting fees from Accord, Janssen, Novartis, Pfizer, and Roche; 
      payment or honoraria for lectures, presentations, speakers bureaus, manuscript 
      writing or educational events from Accord, Janssen, Novartis, Pfizer, and Roche; 
      and participation on a Data Safety Monitoring Board or Advisory Board for 
      Myovant. Peter S. Conti reports no other conflicts to declare. Cora N. Sternberg 
      reports consulting fees from Pfizer, MSD, AZ, Astellas, Sanofi, Genzyme, 
      Roche-Genentech, BMS, Bayer, Foundation Medicine, Gilead, Medscape, UroToday, CCN 
      Clinical, Janssen, NCI (all ad boards over at least 5 years). Fred Saad reports 
      grants or contracts from Astellas, AstraZeneca, Janssen, Myovant, Merck, 
      Novartis, Sanofi, and Pfizer (payment to institution); consulting fees from 
      Amgen, Astellas, AstraZeneca, Bayer, Janssen, Myovant, Merck, Novartis, Sanofi, 
      Pfizer, Tolmar (payment to self); payment or honoraria for lectures, 
      presentations, speakers bureaus, manuscript writing or educational events from 
      Amgen, Astellas, AstraZeneca, Bayer, Janssen, Myovant, Merck, Novartis, Sanofi, 
      Pfizer, Tolmar (payment to self). Juan Pablo Sade reports no other conflicts to 
      declare. Joaquim Bellmunt reports royalties or licenses from UpToDate; consulting 
      fees from Pfizer/MSD, Genentech, AstraZeneca, and Merck; payment or honoraria for 
      lectures, presentations, speakers bureaus, manuscript writing or educational 
      events from Pfizer/MSD, Genentech, AstraZeneca, and Merck; support for attending 
      meetings and/or travel from Pfizer; participation on a Data Safety Monitoring 
      Board or Advisory Board from Pfizer/MSD, Genentech, AstraZeneca, and Merck. 
      Matthew R. Smith reports grants or contracts from Bayer for the present study 
      (paid to self and institution) and from Astellas, Bayer, Janssen, Lilly, and 
      Pfizer (all paid to institution); consulting fees from Astellas, Bayer, Janssen, 
      Lilly, and Pfizer (all paid to self); payment or honoraria for lectures, 
      presentations, speakers bureaus, manuscript writing or educational events from 
      Astellas, Bayer, Janssen, Lilly, and Pfizer (all paid to self); and participation 
      on a Data Safety Monitoring Board or Advisory Board for Bayer, Janssen, and Lilly 
      (all paid to self). Kumari Chandrawansa reports stock or stock options in Bayer; 
      other financial or non-financial interests: employee of Bayer. Per Sandstrom 
      reports other financial or non-financial interests: employee of Bayer. Frank 
      Verholen reports other financial or non-financial interests: employee of Bayer. 
      Bertrand Tombal reports support for the present manuscript from Bayer (support of 
      study); grants or contracts from Bayer (grant for studies); consulting fees from 
      Astellas, Bayer, Novartis, Janssen, Accor, and MSD (all payments to his company: 
      UROADVISE); and payment or honoraria for lectures, presentations, speakers 
      bureaus, manuscript writing or educational events from Bayer (paid to his 
      company: UROADVISE) and Astellas.
EDAT- 2023/05/30 13:07
MHDA- 2023/05/30 13:08
PMCR- 2023/05/18
CRDT- 2023/05/30 11:42
PHST- 2022/11/04 00:00 [received]
PHST- 2023/04/18 00:00 [revised]
PHST- 2023/04/18 00:00 [accepted]
PHST- 2023/05/30 13:08 [medline]
PHST- 2023/05/30 13:07 [pubmed]
PHST- 2023/05/30 11:42 [entrez]
PHST- 2023/05/18 00:00 [pmc-release]
AID - S2589-5370(23)00170-0 [pii]
AID - 101993 [pii]
AID - 10.1016/j.eclinm.2023.101993 [doi]
PST - epublish
SO  - EClinicalMedicine. 2023 May 18;60:101993. doi: 10.1016/j.eclinm.2023.101993. 
      eCollection 2023 Jun.