CHICAGO, IL USA (UroToday.com) - Presented by Emmanuel S. Antonarakis,1 Adam S. Kibel,2 George Adams,3 Lawrence I. Karsh,4 Aymen Elfiky,2 Neal D. Shore,5 Nicholas J. Vogelzang,6 John M. Corman,7 Robert C. Tyler,8 Candice McCoy,8 Yang Wang,8 Nadeem Sheikh,8 and Charles G. Drake1, 9 at the American Society of Clinical Oncology (ASCO) Annual Meeting - May 31 - June 4, 2013 - McCormick Place - Chicago, IL USA
1Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; 2Brigham and Women’s Hospital, Harvard University, Boston, MA; 3Urology Center of Alabama, Homewood, AL; 4The Urology Center of Colorado; 5Carolina Urologic Research Center, Myrtle Beach, SC 6US Oncology Research, Comprehensive Cancer Centers of Nevada, Las Vegas, NV; 7Virginia Mason Medical Center, Seattle, WA; 8Dendreon Corporation, Seattle, WA; 9Brady Urological Institute, Johns Hopkins University, Baltimore, MD
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
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
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 (IFNg, 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; P5.086), 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.