Re-treatment with radium-223: first experience from an international, open-label, phase I/II study in patients with castration-resistant prostate cancer and bone metastases

Six radium-223 injections at 4-week intervals is indicated for patients with castration-resistant prostate cancer and symptomatic bone metastases. However, patients usually develop disease progression after initial treatment. This prospective phase I/II study assessed re-treatment safety and efficacy of up to six additional radium-223 injections.

Patients had castration-resistant prostate cancer and bone metastases and six initial radium-223 injections with no on-treatment bone progression; all had subsequent radiologic or clinical progression. Concomitant agents were allowed at investigator discretion, excluding chemotherapy and initiation of new abiraterone or enzalutamide. The primary endpoint was safety; additional exploratory endpoints included time to radiographic bone progression, time to total alkaline phosphatase and prostate-specific antigen progression, radiographic progression-free survival, overall survival, time to first symptomatic skeletal event (SSE), SSE-free survival, and time to pain progression.

Among 44 patients, 29 (66%) received all six re-treatment injections. Median time from end of initial radium-223 treatment was 6 months. Forty-one (93%) reported ≥1 treatment-emergent adverse event. No grade 4-5 hematologic treatment-emergent adverse events occurred. Only one (2%) patient had radiographic bone progression; eight (18%) had radiographic soft tissue tumor progression (three lymph node and five visceral metastases). Median times to total alkaline phosphatase and prostate-specific antigen progression were not reached and 2.2 months, respectively. Median radiographic progression-free survival was 9.9 months (12.8-month maximum follow-up). Five (11%) patients died and eight (18%) experienced first SSEs. Median overall survival, time to first SSE, and SSE-free survival were not reached. Five (14%) of 36 evaluable patients (baseline worst pain score ≤7) had pain progression. After 2 years of follow-up, 28 (64%) patients died, and the median overall survival was 24.4 months.

Re-treatment with a second course of six radium-223 injections after disease progression is well tolerated, with minimal hematologic toxicity and low radiographic bone progression rates in this small study with limited follow-up. Favorable safety and early effects on disease progression indicate that radium-223 re-treatment is feasible and warrants further evaluation in larger prospective trials.

Annals of oncology : official journal of the European Society for Medical Oncology. 2017 Oct 01 [Epub]

O Sartor, D Heinrich, N Mariados, M J Méndez Vidal, D Keizman, C Thellenberg Karlsson, A Peer, G Procopio, S J Frank, K Pulkkanen, E Rosenbaum, S Severi, J M Trigo Perez, V Wagner, R Li, L T Nordquist

Departments of Medicine and Urology, Tulane Cancer Center, New Orleans, USA., Department of Oncology, Akershus University Hospital, Lørenskog, Norway., Department of Radiation Oncology, Associated Medical Professionals of New York, PLLC, Syracuse, USA., Oncology Department, Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofia Hospital, University of Cordoba, Cordoba, Spain., Genitourinary Oncology Service, Meir Medical Center, Kfar Saba, Israel., Department of Radiation Sciences, Cancer Center Norrlands University, Umeå, Sweden., Division of Oncology, Rambam Health Care Campus, Haifa, Israel., Fondazione Istituto Nazionale Tumori Oncologia Medica Genitourinaria, Milan, Italy., Department of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel., Department of Oncology, Kuopio University Hospital, Kuopio, Finland., Uro-Oncology Unit, Rabin Medical Center-Davidoff Center, Petah Tikva, Israel., Romagnolo Scientific Institute for the Study and Care of Cancer-IRST IRCCS, Nuclear Medicine Therapeutic Unit, Meldola, Italy., Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain., Global Clinical Development, Bayer Pharma AG, Basel, Switzerland., Global Research and Development Statistics, Bayer HealthCare Pharmaceuticals, Whippany., Department of Medical Oncology, GU Research Network, LLC, Omaha, USA.