TY - JOUR
T1 - Randomized phase II trial of sipuleucel-T with or without radium-223 in men with bone-metastatic castration-resistant prostate cancer
AU - Marshall, Catherine H.
AU - Fu, Wei
AU - Wang, Hao
AU - Park, Jong Chul
AU - DeWeese, Theodore L.
AU - Tran, Phuoc T.
AU - Song, Daniel Y.
AU - King, Serina
AU - Afful, Michaella
AU - Hurrelbrink, Julia
AU - Manogue, Charlotte
AU - Cotogno, Patrick
AU - Moldawer, Nancy P.
AU - Barata, Pedro C.
AU - Drake, Charles G.
AU - Posadas, Edwin M.
AU - Armstrong, Andrew J.
AU - Sartor, Oliver
AU - Antonarakis, Emmanuel S.
N1 - Funding Information:
This study was funded by Dendreon Corporation. Radium-223 was provided free of charge by Bayer Pharmaceuticals. Support was also received from the NIH Cancer Center support grant P30CA006973.
Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-20-4476
DO - 10.1158/1078-0432.CCR-20-4476
M3 - Article
C2 - 33451978
AN - SCOPUS:85102850915
SN - 1078-0432
VL - 27
SP - 1623
EP - 1630
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 6
ER -