A randomized phase II study evaluating the optimal sequencing of sipuleucel-T and androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC): Immune results.

Genitourinary (Prostate) Cancer
Session Type and Session Title: 
Poster Discussion Session, Genitourinary (Prostate) Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 5016)
Emmanuel S. Antonarakis, Adam S Kibel, George Adams, Lawrence Ivan Karsh, Aymen Elfiky, Neal D. Shore, Nicholas J. Vogelzang, John M. Corman, Robert Claude Tyler, Candice McCoy, Yang Wang, Nadeem A. Sheikh, Charles G. Drake; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Brigham and Women's Hospital/Harvard University, Boston, MA; Urology Centers of Alabama, Homewood, AL; The Urology Center of Colorado, Denver, CO; Carolina Urologic Research Center, Myrtle Beach, SC; Comprehensive Cancer Centers of Nevada, The US Oncology Network, Las Vegas, NV; Virginia Mason Medical Center, Seattle, WA; Dendreon Corporation, Seattle, WA

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Abstract Disclosures


Background: ADT is a standard treatment for men with BRPC after failure of local therapy, and has immunomodulatory effects. Sipuleucel-T is an autologous cellular immunotherapy approved for asymptomatic/minimally symptomatic metastatic castrate resistant prostate cancer. The STAND trial (NCT01431391) aimed to evaluate optimal sequencing of sipuleucel-T and ADT in men with BRPC at high risk for metastases (ie PSA doubling time ≤12 mo). Methods: Men were randomized (1:1) to Arm 1: sipuleucel-T followed by ADT (2 wks after 3rd infusion); or Arm 2: ADT (3 mo lead in) followed by sipuleucel-T. All men had 3 doses of sipuleucel-T and 12 mo of ADT (45 mg leuprolide SQ at 6 mo intervals). The primary endpoint is cellular immune response (ELISPOT to PA2024 [PAP-GMCSF]). Secondary endpoints are humoral and cytokine responses, product parameters and safety. Results: 68 men were randomized. Preliminary data show higher levels of serum cytokines in Arm 2 vs Arm 1, with a pattern suggesting a mixed TH1/TH2 cellular immune response; elevations were seen in TH1 (IFNγ, IL 12), TH2 (IL 4, 5, 10, 13) and TH17 (IL 17) subsets (all P<.05). The increase in TH1 cytokines was consistent with a trend toward higher PA2024-specific ELISPOT responses 2 wk after the 3rd sipuleucel-T infusion in Arm 2 vs Arm 1 (40.5 vs 12.8 spots; P=.086), suggesting increased T cell activation in Arm 2. Antigen-specific humoral responses were induced in both arms with no differences yet observed between arms. Sipuleucel-T product parameters were roughly equivalent in both arms with APC activation data indicating a robust prime-boost effect. Conclusions: While confirmation is required, these preliminary data suggest that tumor-specific T cell responses and broad based immune responses are augmented when sipuleucel-T is given after rather than before ADT initiation. These data are consistent with preclinical studies showing that ADT enhances T cell activity, and provide preliminary evidence that combining ADT with sipuleucel-T may augment adaptive immunity. Further follow up will determine whether augmented immune responses correlate with clinical parameters (eg PSA recurrence). Clinical trial information: NCT01431391.