To investigate if radium-223 increases peripheral immune responses to sipuleucel-T in men with bone-predominant, minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).
32 patients were randomized 1:1 in this open label, phase 2 multicenter trial. Patients in the control arm received 3 sipuleucel-T treatments, 2 weeks apart. Those in the combination arm received 6 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 to those who received combination treatment (p=0.036). Patients in the combination arm were more likely to have a >50% PSA decline (5 (31%) versus 0 patients; P=0.04), and also demonstrated longer PFS (39 vs 12 weeks; HR 0.32; 95% 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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Jan 15 [Epub ahead of print]
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 E Manogue, Patrick Cotogno, Nancy P Moldawer, Pedro Barata, Charles G Drake, Edwin M Posadas, Andrew J Armstrong, Oliver Sartor, Emmanuel S Antonarakis
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine., Oncology, Johns Hopkins University School of Medicine., Biostatistics and Bioinformatics, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center., Hematology and Oncology, Massachusetts General Hospital., Radiation Oncology, Johns Hopkins University School of Medicine., Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine., Oncology, Sidney Kimmel Comprehensive Cancer Center., Divisions of Medical Oncology and Urology, Departments of Medicine and Surgery, Duke Cancer Institute., Tulane Medical Center., Medicine and Urology, Tulane University., Urologic Oncology Program, Cedars-Sinai Medical Center., Deming Department of Medicine, Tulane University., Department of Urology, and the Columbia Center for Translational Immunology (CCTI), Columbia University Herbert Irving Comprehensive Cancer Center., Urologic Oncology Program & Uro-Oncology Research Laboratories, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center., Medicine and Urology, Tulane University School of Medicine., Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine .