Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men with Hormone-Sensitive Biochemically Recurrent Prostate Cancer: A Phase II Randomized Trial.
Purpose: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.Experimental Design:Men with BRPC following prostatectomy and/or radiotherapy, a PSA doubling time ≤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.Results: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= 0.001). PA2024-specific cellular and humoral responses and prostatic acid phosphatase-specific humoral responses increased significantly versus baseline (P< 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 (HR, 0.22; 95% CI, 0.08-0.67;P= 0.007). Sipuleucel-T with ADT was generally well tolerated.Conclusions:Sipuleucel-T→ADT appears to induce greater antitumor immune responses than the reverse sequence. These results warrant further investigation to determine whether this sequence leads to improved clinical outcomes, as well as the independent contribution of ADT alone in terms of immune activation.Clin Cancer Res; 23(10); 2451-9. ©2016 AACR.
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC), Baltimore, Maryland.
Emmanuel S
ES
Antonarakis
Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts.
Adam S
AS
Kibel
University of Washington and Seattle Cancer Care Alliance, Seattle, Washington.
Evan Y
EY
Yu
The Urology Center of Colorado, Denver, Colorado.
Lawrence I
LI
Karsh
Dana-Farber Cancer Institute, Boston, Massachusetts.
Aymen
A
Elfiky
Carolina Urologic Research Center, Myrtle Beach, South Carolina.
Neal D
ND
Shore
US Oncology Research Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada.
Nicholas J
NJ
Vogelzang
Virginia Mason Medical Center, Seattle, Washington.
John M
JM
Corman
Moores UCSD Cancer Center, La Jolla, California.
Frederick E
FE
Millard
Dendreon Pharmaceuticals Inc., Seattle, Washington.
Johnathan C
JC
Maher
Dendreon Pharmaceuticals Inc., Seattle, Washington.
Nancy N
NN
Chang
Dendreon Pharmaceuticals Inc., Seattle, Washington.
Todd
T
DeVries
Dendreon Pharmaceuticals Inc., Seattle, Washington.
Nadeem A
NA
Sheikh
Johns Hopkins SKCCC, the Brady Urological Institute and the Bloomberg Kimmel Institute, Baltimore, Maryland. cgd2139@cumc.columbia.edu.
Charles G
CG
Drake
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000276:immunology; D000728:Androgens / Q000378:metabolism*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014020:Tissue Extracts / Q000008:administration & dosage* / Q000276:immunology
D000726:Androgen Antagonists; D000728:Androgens; D019496:Cancer Vaccines; D014020:Tissue Extracts; C511774:sipuleucel-T; D017430:Prostate-Specific Antigen