Randomized phase II trial of sipuleucel-T with or without radium-223 in men with bone-metastatic castration-resistant prostate cancer

Catherine H. Marshall, Wei Fu, Hao Wang, Jong Chul Park, Theodore L. DeWeese, Phuoc T. Tran, Daniel Y. Song, Serina King, Michaella Afful, Julia Hurrelbrink, Charlotte Manogue, Patrick Cotogno, Nancy P. Moldawer, Pedro C. Barata, Charles G. Drake, Edwin M. Posadas, Andrew J. Armstrong, Oliver Sartor, Emmanuel S. Antonarakis

Research output: Contribution to journalArticlepeer-review


Purpose: To investigate whether radium-223 increases peripheral immune responses to sipuleucel-T in men with bone-predominant, minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods: A total of 32 patients were randomized 1:1 in this open-label, phase II multicenter trial. Patients in the control arm received three sipuleucel-T treatments, 2 weeks apart. Those in the combination arm received six doses of radium-223 monthly, with sipuleucel-T intercalated between the second and fourth doses of radium-223. The primary endpoint was a comparison of peripheral antigen PA2024-specific T-cell responses (measured by proliferation index). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and PSA responses. Results: We enrolled 32 patients, followed for a median of 1.6 years. Six weeks after the first sipuleucel-T dose, participants in the control arm had a 3.2-fold greater change in PA2024-specific T-cell responses compared with those who received combination treatment (P ¼ 0.036). Patients in the combination arm were more likely to have a >50% PSA decline [5 (31%) vs. 0 patients; P ¼ 0.04], and also demonstrated longer PFS [39 vs. 12 weeks; HR, 0.32; 95% confidence interval (CI), 0.14-0.76] and OS (not reached vs. 2.6 years; HR, 0.32; 95% CI, 0.08-1.23). Conclusions: Our data raise the possibility of greater clinical activity with the combination of sipuleucel-T and radium-223 in men with asymptomatic bone mCRPC, despite the paradoxically lower immune responses observed. Additional study to confirm these findings in a larger trial is warranted.

Original languageEnglish (US)
Pages (from-to)1623-1630
Number of pages8
JournalClinical Cancer Research
Issue number6
StatePublished - Mar 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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