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Clin Cancer Res. 2015 Sep 1;21(17):3862-9. doi: 10.1158/1078-0432.CCR-15-0079. Epub 2015 Apr 29.

A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer.

Author information

1
UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California. smalle@medicine.ucsf.edu.
2
Eastern Virginia Medical School/Urology of Virginia PLLC, Norfolk, Virginia.
3
Department of Urology at Indiana University School of Medicine, Indianapolis, Indiana.
4
The Urology Center of Colorado, Denver, Colorado.
5
UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
6
Dendreon Pharmaceuticals, Inc., Seattle, Washington.
7
Sharp Clinical Oncology Research, San Diego, California.
8
Carolina Urologic Research Center, Myrtle Beach, South Carolina.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

PMID:
25925891
DOI:
10.1158/1078-0432.CCR-15-0079
[Indexed for MEDLINE]
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