Immune responses and clinical outcomes in STAND, a randomized phase 2 study evaluating optimal sequencing of sipuleucel-T (sip-T) and androgen deprivation therapy (ADT) in biochemically-recurrent prostate cancer (BRPC) after local therapy failure.

Authors

null

Emmanuel S. Antonarakis

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD

Emmanuel S. Antonarakis , Adam S. Kibel , George W. Adams , Lawrence Ivan Karsh , Aymen Elfiky , Neal D. Shore , Nicholas J. Vogelzang , John M. Corman , Johnathan Cartwright Maher , Todd DeVries , Candice McCoy , Nadeem A. Sheikh , Charles G. Drake

Organizations

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, Brigham and Women's Hospital, Harvard University, Urologic Surgery, Boston, MA, Urology Centers of Alabama, Urology, Homewood, AL, The Urology Center of Colorado, Clinical Research, Denver, CO, Dana-Farber Cancer Institute, Boston, MA, Carolina Urologic Research Center, Myrtle Beach, SC, US Oncology Research Comprehensive Cancer Centers of Nevada, Las Vegas, NV, Virginia Mason Hospital & Seattle Medical Center, Seattle, WA, Dendreon Corporation, Seattle, WA, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Oncology, Baltimore, MD

Research Funding

Pharmaceutical/Biotech Company

Background: STAND (NCT01431391) assessed optimal sequencing of sip-T and ADT in men with BRPC at high risk of metastases after local therapy (i.e. prostate specific antigen doubling time [PSADT] < 12 mo). Methods: Men (n = 68) were randomized to sip-T then ADT (2 wks post infusion 3; Arm 1) or ADT (3 mo lead-in) then sip-T (Arm 2). Cellular and humoral immune responses, and clinical outcomes were analyzed. PSA recurrence was defined as ≥ 2 serial rises in PSA and an absolute PSA value of ≥ 0.2 ng/mL (prior radical prostatectomy) or ≥ 2.0 ng/mL (prior radiotherapy alone). PSADT post-ADT was analyzed. Time to next anticancer intervention (TTACI) was measured from first ADT to the day of the next systemic therapy. Rate of metastases at 24 mo was also investigated. Results: All men received 3 sip-T doses, and 96% received 12 mo ADT. Cellular and humoral responses to PA2024 increased following treatment vs baseline (BL) and were sustained at all post-sip-T timepoints through 24 mo (p < 0.05). PA2024-specific T cell proliferation responses were higher in Arm 1 vs Arm 2 (p<0.001). The number of PA2024 antibody (Ab) responders (post-BL Ab titer ≥ 25,600) was similar between arms. Sip-T-mediated antigen spread was observed in both arms vs BL and maintained through 24 mo (p < 0.001). No significant differences between arms were observed in clinical outcomes: median time to PSA recurrence (21.8 vs 22.6 mo, HR: 0.70, 95% CI: 0.39–1.28; p = 0.357), PSADT (2.54 vs 2.58 mo, p = 0.944), metastases at 24 mo (6/31 vs 3/26, p = 0.419), or TTACI (medians not reached, p = 0.199). However, across the entire cohort, PA2024 Ab responses correlated with longer time to PSA recurrence (p = 0.007). Adverse events occurring in >20% were hot flashes, fatigue, headache, and chills. Conclusions: In men with non-metastatic BRPC, sip-T + 12 mo ADT induced a robust immune response that persisted for 24 mo. Data suggest a greater anti-PA2024 T cell proliferative response in Arm 1 (sip-T then ADT). Induction of a PA2024 Ab response may correlate with longer time to PSA progression. Clinical trial information: NCT01431391

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Abstract Details

Meeting

2015 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Genitourinary (Prostate) Cancer

Track

Genitourinary Cancer

Sub Track

Prostate Cancer

Clinical Trial Registration Number

NCT01431391

Citation

J Clin Oncol 33, 2015 (suppl; abstr 5030)

DOI

10.1200/jco.2015.33.15_suppl.5030

Abstract #

5030

Poster Bd #

22

Abstract Disclosures