Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men with Hormone-Sensitive Biochemically-Recurrent Prostate Cancer: A Phase II Randomized Trial

STAND, a randomized, phase II, open-label trial (NCT01431391) assessed sequencing of sipuleucel-T (an autologous cellular immunotherapy) with androgen deprivation therapy (ADT) in biochemically-recurrent prostate cancer (BRPC) patients at high risk for metastasis.

Men with BRPC following prostatectomy and/or radiotherapy, a prostate-specific antigen (PSA) doubling time (PSADT)less than or equal to 12 months, and no metastasis were enrolled. Patients were randomized (34/arm) to sipuleucel-T followed by ADT (started 2 weeks after sipuleucel-T completion), or ADT followed by sipuleucel-T (started 12 weeks after ADT initiation); ADT continued for 12 months in both arms. The primary endpoint was PA2024-specific T cell response (Enzyme-Linked ImmunoSPOT [ELISPOT]) over time.

PA2024-specific ELISPOT responses over time were similar between groups, except at week 6, where responses were higher with sipuleucel-T→ADT versus ADT→sipuleucel-T (P=0.013). PA2024-specific T cell proliferation responses, averaged across time points, were approximately 2-fold higher with sipuleucel-T→ADT versus ADT→sipuleucel-T (P equals 0.001). PA2024-specific cellular and humoral responses, and prostatic acid phosphatase-specific humoral responses increased significantly versus baseline (P less than 0.001), and were maintained for 24 months (both arms). Median time-to-PSA recurrence was similar between arms (21.8 vs. 22.6 months, P=0.357). Development of a PA2024-specific humoral response correlated with prolonged time-to-PSA progression (hazard ratio 0.22, 95% CI 0.08 to 0.67; P=0.007). Sipuleucel-T with ADT was generally well-tolerated.

Sipuleucel-T→ADT appears to induce greater antitumor immune responses than the reverse sequence. These results warrant further investigation to determine if this sequence leads to improved clinical outcomes, as well as the independent contribution of ADT alone in terms of immune activation.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2016 Nov 10 [Epub ahead of print]

Emmanuel S Antonarakis, Adam S Kibel, Evan Y Yu, Lawrence I Karsh, Aymen Elfiky, Neal D Shore, Nicholas J Vogelzang, John M Corman, Frederick E Millard, Johnathan C Maher, Nancy Chang, Todd DeVries, Nadeem A Sheikh, Charles G Drake

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine., Division of Urology, Brigham and Women's Hospital., Medicine (Oncology), University of Washington and Fred Hutchinson Cancer Research Center., Urology, The Urology Center of Colorado., Medicine, Harvard University., Carolina Urologic Research Center., Medical Oncology, US Oncology/Comprehensive Cancer Centers of Nevada., Urology, Virginia Mason Medical Center., Medicine, University of California, San Diego., Oncology Global Medical Affairs, Abbvie Inc., Medical Affairs, Dendreon Corporation., Research, Dendreon., Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine .