A randomized phase II trial of sipuleucel-T with concurrent versus sequential abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer

Eric J. Small, Raymond S. Lance, Thomas Gardner, Lawrence I. Karsh, Lawrence Fong, Candice McCoy, Todd De Vries, Nadeem A. Sheikh, Debraj GuhaThakurta, Nancy Chang, Charles H. Redfern, Neal D. Shore

Research output: Contribution to journalArticle

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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 end-points 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. Inboth 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.

Original languageEnglish (US)
Pages (from-to)3862-3869
Number of pages8
JournalClinical Cancer Research
Volume21
Issue number17
DOIs
StatePublished - Sep 1 2015

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Castration
Prednisone
Prostatic Neoplasms
Antigen-Presenting Cells
Cell Count
Safety
Antigens
Abiraterone Acetate
sipuleucel-T
Research Design
Cell Proliferation
T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A randomized phase II trial of sipuleucel-T with concurrent versus sequential abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer. / Small, Eric J.; Lance, Raymond S.; Gardner, Thomas; Karsh, Lawrence I.; Fong, Lawrence; McCoy, Candice; De Vries, Todd; Sheikh, Nadeem A.; GuhaThakurta, Debraj; Chang, Nancy; Redfern, Charles H.; Shore, Neal D.

In: Clinical Cancer Research, Vol. 21, No. 17, 01.09.2015, p. 3862-3869.

Research output: Contribution to journalArticle

Small, EJ, Lance, RS, Gardner, T, Karsh, LI, Fong, L, McCoy, C, De Vries, T, Sheikh, NA, GuhaThakurta, D, Chang, N, Redfern, CH & Shore, ND 2015, 'A randomized phase II trial of sipuleucel-T with concurrent versus sequential abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer', Clinical Cancer Research, vol. 21, no. 17, pp. 3862-3869. https://doi.org/10.1158/1078-0432.CCR-15-0079
Small, Eric J. ; Lance, Raymond S. ; Gardner, Thomas ; Karsh, Lawrence I. ; Fong, Lawrence ; McCoy, Candice ; De Vries, Todd ; Sheikh, Nadeem A. ; GuhaThakurta, Debraj ; Chang, Nancy ; Redfern, Charles H. ; Shore, Neal D. / A randomized phase II trial of sipuleucel-T with concurrent versus sequential abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer. In: Clinical Cancer Research. 2015 ; Vol. 21, No. 17. pp. 3862-3869.
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AU - Lance, Raymond S.

AU - Gardner, Thomas

AU - Karsh, Lawrence I.

AU - Fong, Lawrence

AU - McCoy, Candice

AU - De Vries, Todd

AU - Sheikh, Nadeem A.

AU - GuhaThakurta, Debraj

AU - Chang, Nancy

AU - Redfern, Charles H.

AU - Shore, Neal D.

PY - 2015/9/1

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N2 - 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 end-points 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. Inboth 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.

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