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.

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.

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.

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.

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.

Bayer HealthCare.

EClinicalMedicine. 2023 May 18*** epublish ***

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

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