Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial

In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment.

To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection.

Safety analyses from phase 3 randomized ALSYMPCA trial included patients receiving ≥1 study-drug injection (600 radium-223 and 301 placebo). Patients (405 radium-223 and 167 placebo) entered long-term safety follow-up starting 12 wk after the last study-drug injection, to 3 yr from the first injection. Forty-eight of 405 (12%) radium-223 and 12/167 (7%) placebo patients completed follow-up, with evaluations every 2 mo for 6 mo, then every 4 mo until 3 yr.

All adverse events (AEs) were collected until 12 wk after the last injection; subsequently, only treatment-related AEs were collected. Additional long-term safety was assessed by development of acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia, and secondary malignancies. Data analysis used descriptive statistics.

During treatment to 12 wk following the last injection, 564/600 (94%) radium-223 and 292/301 (97%) placebo patients had treatment-emergent AEs (TEAEs). Myelosuppression incidence was low. Grade 3/4 hematologic TEAEs in radium-223 and placebo groups were anemia (13% vs 13%), neutropenia (2% vs 1%), and thrombocytopenia (7% vs 2%). Ninety-eight of 600 (16%) radium-223 and 68/301 (23%) placebo patients experienced grade 5 TEAEs. Long-term follow-up showed no AML, MDS, or new primary bone cancer; secondary non-treatment-related malignancies occurred in four radium-223 and three placebo patients. One radium-223 patient had aplastic anemia 16 mo after the last injection. No other cases were observed. Limitations include short (3-yr) follow-up.

Final long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated, with low myelosuppression incidence and no new safety concerns.

Updated Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial findings show that radium-223 remained well tolerated during treatment and up to 3 yr after each patient's first injection.

European urology. 2017 Jul 10 [Epub ahead of print]

Christopher C Parker, Robert E Coleman, Oliver Sartor, Nicholas J Vogelzang, David Bottomley, Daniel Heinrich, Svein I Helle, Joe M O'Sullivan, Sophie D Fosså, Aleš Chodacki, Paweł Wiechno, John Logue, Mihalj Seke, Anders Widmark, Dag Clement Johannessen, Peter Hoskin, Nicholas D James, Arne Solberg, Isabel Syndikus, Jan Kliment, Steffen Wedel, Sibylle Boehmer, Marcos Dall'Oglio, Lars Franzén, Øyvind S Bruland, Oana Petrenciuc, Karin Staudacher, Rui Li, Sten Nilsson

The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK. Electronic address: ., University of Sheffield, Weston Park Hospital, Sheffield, UK., Tulane Cancer Center, New Orleans, LA, USA., Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA., St James's University Hospital, Leeds, UK., Akershus University Hospital, Lørenskog, Norway., Haukeland University Hospital, Bergen, Norway., Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK., Radiumhospitalet, Oslo, Norway., Hospital Kochova, Chomutov, Czech Republic., Centrum Onkologii-Instytut im Sklodowskiej-Curie, Warsaw, Poland., Christie Hospital, Manchester, UK., Centrallasarettet Växjö, Växjö, Sweden., Umeå University, Umeå, Sweden., Ullevål University Hospital, Oslo, Norway., Mount Vernon Hospital Cancer Centre, Middlesex, UK., Cancer Centre, University Hospitals Birmingham NHS Trust, Birmingham, UK., St Olavs Hospital, Trondheim, Norway., Clatterbridge Center for Oncology, Wirral, UK., Jessenius School of Medicine, Comenius University, University Hospital, Martin, Slovakia., Department of Urology, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany., Gemeinschaftspraxis, Berlin, Germany., Hospital das Clínicas, Faculdade de Medicina da USP, Instituto do Câncer do Estado de São Paulo, Brazil., Länssjukhuset Sundsvall-Härnösand County Hospital, Sundsvall, Sweden; Umeå University Hospital, Umeå, Sweden., Norwegian Radium Hospital Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway., Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA., Bayer AS (formerly Algeta ASA), Oslo, Norway., Karolinska University Hospital, Stockholm, Sweden.