STOCKHOLM, SWEDEN (UroToday.com) - The primary endpoint of this study was cellular immune response (ELISPOT to PA2024 [PAP-GMCSF]) with humoral and cytokine responses, product parameters, and safety being their secondary endpoints. This trial (P10-2 STAND) aimed to evaluate optimal sequencing of sipuleucel-T and ADT in men with BRPC, who were at high risk for metastases (ie., PSA doubling time ≤ 12 months). Men were randomized (1:1) to Arm 1: sipuleucel-T followed by ADT (2 weeks after 3rd infusion) or Arm 2: ADT (3 month lead in) followed by sipuleucel-T. All men received 3 doses of sipuleucel-T and 12 months of ADT (45 mg leuprolide at 6-month intervals).
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A total of 68 men were randomized to the study, with preliminary data showing 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, IL-10, IL-13) and TH17 (IL-17) subsets (all p < 0.05). They reported that increase in TH1 cytokines was consistent with a trend toward higher PA2024-specific ELISPOT responses 2 weeks after the 3rd sipuleucel-T infusion in Arm 2 vs Arm 1 (median of 40.5 vs 12.8 spots; p=0.086), suggesting increased T-cell activation in Arm 2. After 12 weeks, augmented antigen-specific humoral responses (to PA2024 and PAP) were seen and persisted for at least 12 months in both groups.
ADT has been a standard treatment for men with BRPC after failure of local therapy. The U.S. FDA and the European EMA approved sipuleucel-T (an autologous cellular immunotherapy that targets prostatic acid phosphatase) for the treatment of certain men with documented metastatic castration-resistant prostate cancer (mCRPC). The preliminary data from this trial suggest that if sipuleucel-T is given after, rather than before ADT, the initiation of immune and tumor-specific T-cell responses is augmented. Moreover, the augmented humoral responses were persistent for at least 12 months. Results of this clinical trial, with longer follow-up and longer T-cell/cytokine responses, will determine whether seen immune responses correlate with PSA recurrence or other clinical parameters.
Presented by E. S. Antonarakis at the 29th Annual European Association of Urology (EAU) Congress - April 11 - 15, 2014 - Stockholmsmässan - Stockholm, Sweden.
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Dept. of Oncology, Baltimore USA
Written by Reza Mehrazin, MD, medical writer for UroToday.com
Click HERE to listen to an audio commentary by Robert Tyler, PhD, one of the authors of this study
Click HERE to view the poster from this session