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

Celestia S Higano; Daniel J George; Neal D Shore; Oliver Sartor; Kurt Miller; Peter S Conti; Cora N Sternberg; Fred Saad; Juan Pablo Sade; Joaquim Bellmunt; Matthew R Smith; Kumari Chandrawansa; Per Sandström; Frank Verholen; Bertrand Tombal

doi:10.1016/j.eclinm.2023.101993

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

EClinicalMedicine. 2023 May 18:60:101993. doi: 10.1016/j.eclinm.2023.101993. eCollection 2023 Jun.

Authors

Affiliations

¹ Departments of Medicine and Urology, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
² Departments of Medicine and Surgery, Duke Cancer Institute, Duke University, Durham, NC, USA.
³ Carolina Urologic Research Center, Myrtle Beach, SC, USA.
⁴ Departments of Medicine and Urology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA.
⁵ Department of Urology, Charité University Hospital, Berlin, Germany.
⁶ Molecular Imaging Center, Keck School of Medicine of USC, Los Angeles, CA, USA.
⁷ Englander Institute for Precision Medicine, Weill Cornell Department of Medicine, Meyer Cancer Center, New York-Presbyterian Hospital, New York, NY, USA.
⁸ Department of Urology, University of Montreal Hospital Center, Montreal, Quebec, Canada.
⁹ Department of Clinical Oncology, Alexander Fleming Institute, Buenos Aires, Argentina.
¹⁰ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹¹ Genitourinary Oncology Program, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
¹² Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
¹³ Bayer Consumer Care AG, Basel, Switzerland.
¹⁴ Division of Urology, IREC, Cliniques Universitaires Saint Luc, UCLouvain, Brussels, Belgium.

Abstract

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.

Keywords: Clinical outcomes; Metastatic castration-resistant prostate cancer; Radium-223.