A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer.
OBJECTIVE
This phase II open-label study evaluated the effect of concurrent or sequential administration of abiraterone acetate plus prednisone (AA + P) on sipuleucel-T manufacture and immune responses in metastatic castration-resistant prostate cancer (mCRPC) patients.


METHODS
mCRPC patients received sipuleucel-T followed by AA + P 1 day (concurrent) or 10 weeks (sequential) after the first sipuleucel-T infusion. AA + P treatment continued for 26 weeks. The primary endpoint was cumulative antigen presenting cell (APC) activation, and secondary endpoints included cumulative APC number and total nucleated cell counts. Additional endpoints included in vivo peripheral immune responses to sipuleucel-T (T-cell responses, T-cell proliferation, humoral responses, and antigen spread) as well as safety.


RESULTS
Sixty-nine mCRPC patients were enrolled, with 35 and 34 patients randomized to the concurrent and sequential arms, respectively. Ex vivo APC activation was significantly greater at the second and third infusions compared with baseline in both arms (P < 0.05), indicative of an immunologic prime-boost effect. In both arms, sipuleucel-T product parameter profiles and peripheral immune responses were consistent with previously conducted sipuleucel-T phase III trials. Antigen spread was similarly observed in both arms and consistent with the other immunologic endpoints.


CONCLUSIONS
These data suggest that sipuleucel-T can be successfully manufactured during concurrent administration of AA + P without blunting immunologic effects or altering immune parameters that correlate with sipuleucel-T's clinical benefit. Combination of these agents was well tolerated, with no new safety signals emerging.
UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California. smalle@medicine.ucsf.edu.
Eric J
EJ
Small
Eastern Virginia Medical School/Urology of Virginia PLLC, Norfolk, Virginia.
Raymond S
RS
Lance
Department of Urology at Indiana University School of Medicine, Indianapolis, Indiana.
Thomas A
TA
Gardner
The Urology Center of Colorado, Denver, Colorado.
Lawrence I
LI
Karsh
UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
Lawrence
L
Fong
Dendreon Pharmaceuticals, Inc., Seattle, Washington.
Candice
C
McCoy
Dendreon Pharmaceuticals, Inc., Seattle, Washington.
Todd
T
DeVries
Dendreon Pharmaceuticals, Inc., Seattle, Washington.
Nadeem A
NA
Sheikh
Dendreon Pharmaceuticals, Inc., Seattle, Washington.
Debraj
D
GuhaThakurta
Dendreon Pharmaceuticals, Inc., Seattle, Washington.
Nancy
N
Chang
Sharp Clinical Oncology Research, San Diego, California.
Charles H
CH
Redfern
Carolina Urologic Research Center, Myrtle Beach, South Carolina.
Neal D
ND
Shore
D000069501:Abiraterone Acetate / Q000008:administration & dosage; D000368:Aged; D000369:Aged, 80 and over; D000938:Antigen-Presenting Cells / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011241:Prednisone / Q000008:administration & dosage; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014020:Tissue Extracts / Q000008:administration & dosage; D016896:Treatment Outcome
D014020:Tissue Extracts; C511774:sipuleucel-T; D000069501:Abiraterone Acetate; D011241:Prednisone