Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer

• Published in: Clinical cancer research 2021-03, Vol.27 (6), p.1623-1630
• Main Authors: Marshall, Catherine H, Fu, Wei, Wang, Hao, Park, Jong Chul, DeWeese, Theodore L, Tran, Phuoc T, Song, Daniel Y, King, Serina, Afful, Michaella, Hurrelbrink, Julia, Manogue, Charlotte, Cotogno, Patrick, Moldawer, Nancy P, Barata, Pedro C, Drake, Charles G, Posadas, Edwin M, Armstrong, Andrew J, Sartor, Oliver, Antonarakis, Emmanuel S
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Chemoradiotherapy - mortality; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms, Castration-Resistant - pathology; Prostatic Neoplasms, Castration-Resistant - therapy; Radium - therapeutic use; Survival Rate; Tissue Extracts - therapeutic use
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-20-4476

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). 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. 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 ( = 0.036). Patients in the combination arm were more likely to have a >50% PSA decline [5 (31%) vs. 0 patients; = 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). 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.