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

Research output: Contribution to journalArticle

  • External authors:
  • 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
  • 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

Abstract

BACKGROUND: 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.

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

DESIGN, SETTING, AND PARTICIPANTS: 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.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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.

RESULTS AND LIMITATIONS: 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.

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

PATIENT SUMMARY: 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.

Bibliographical metadata

Original languageEnglish
JournalEuropean Urology
Early online date10 Jul 2017
DOIs
Publication statusE-pub ahead of print - 10 Jul 2017