939P - Neoadjuvant sipuleucel-T in localized prostate cancer: effects on immune cells within the prostate tumor microenvironment

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Prostate Cancer
Immunotherapy
Therapy
Presenter Lawrence Fong
Authors L. Fong1, V. Weinberg2, S.E. Chan2, J. Corman3, C. Amling4, R.A. Stephenson5, J. Simko2, R. Sims6, P. Carroll2, E.J. Small2
  • 1University of California, San Francisco, 94143 - San Francisco/US
  • 2Comprehensive Cancer Center, University of California, San Francisco, 94143 - San Francisco/US
  • 3Surgery, Virginia Mason Medical Center, 98111 - Seattle/US
  • 4Urology, Oregon Health & Science University, Portland/US
  • 5Urology, University of Utah, Salt Lake City/US
  • 6Clinical Affairs, Dendreon Corporation, Seattle/US

Abstract

Background

Sipuleucel-T is an FDA-approved autologous cellular immunotherapy for patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC). To date, studies of sipuleucel-T in patients with mCRPC have studied immune response in peripheral blood. The immune effects of sipuleucel-T in prostatic cancer tissue are unknown.

Methods

NeoACT (P07-1; NCT00715104) is an open-label, Phase 2 study of patients with localized prostate cancer who received sipuleucel-T prior to radical prostatectomy (RP) to examine the immunologic effects of treatment on prostate tissue. Patients received 3 infusions of sipuleucel-T at approximately 2-week intervals, beginning 6-7 weeks prior to RP, and post-RP are being followed for immune response. The primary endpoint was the change in the frequency of lymphocytes between prostate biopsies (pre-treatment) and RP tissue (post-treatment), as assessed by immunohistochemistry (IHC).

Results

Of the 42 enrolled patients (median age 61 years, all ECOG = 0, Gleason Sum: ≤6 = 24%, 7 = 43%, ≥8 = 33%), 38 received all 3 pre-RP sipuleucel-T infusions and were evaluable by IHC. Treatment-related AEs were manageable and transient. Sipuleucel-T did not appear to affect operative complications, procedure time, or estimated blood loss. Frequent events (>10% of patients) that occurred ≤1 day after infusion were fatigue, headache, and myalgia. Significant increases (>3 fold) in infiltrating CD3 + , CD3 + /CD4 + , and CD3 + /CD8+ T cell populations were observed at the tumor rim (where benign and malignant glands interface), compared with the pretreatment biopsy (all p = 0.0001). CD3 + /CD4 + /FoxP3+ cells were also increased at the tumor rim (∼2-fold; P = 0.005), but represented a small proportion of the observed T cells. This level of T cell infiltration was not seen in a cohort of 12 concurrent cases that did not receive neoadjuvant treatment.

Conclusions

Neoadjuvant sipuleucel-T treatment is associated with an increased frequency of T cells in the prostate at the interface of the benign and malignant glands. These data demonstrate that sipuleucel-T can modulate the presence of lymphocytes at prostate cancer tissue in vivo.

Disclosure

L. Fong: Research funding from Dendreon.

R.B. Sims: Employee and stockholder of Dendreon.

P. Carroll: Honoraria from Takeda. Research funding from Myriad and Abbot,

E.J. Small: Honoraria from Dendreon.

All other authors have declared no conflicts of interest.