Cancer Immunology, Immunotherapy

, Volume 59, Issue 5, pp 663–674

Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer

  • James L. Gulley
  • Philip M. Arlen
  • Ravi A. Madan
  • Kwong-Yok Tsang
  • Mary P. Pazdur
  • Lisa Skarupa
  • Jacquin L. Jones
  • Diane J. Poole
  • Jack P. Higgins
  • James W. Hodge
  • Vittore Cereda
  • Matteo Vergati
  • Seth M. Steinberg
  • Susan Halabi
  • Elizabeth Jones
  • Clara Chen
  • Howard Parnes
  • John J. Wright
  • William L. Dahut
  • Jeffrey Schlom
Original Article

DOI: 10.1007/s00262-009-0782-8

Cite this article as:
Gulley, J.L., Arlen, P.M., Madan, R.A. et al. Cancer Immunol Immunother (2010) 59: 663. doi:10.1007/s00262-009-0782-8

Abstract

A concurrent multicenter, randomized Phase II trial employing a recombinant poxviral vaccine provided evidence of enhanced median overall survival (OS) (p = 0.0061) in patients with metastatic castrate-resistant prostate cancer (mCRPC). The study reported here employed the identical vaccine in mCRPC to investigate the influence of GM-CSF with vaccine, and the influence of immunologic and prognostic factors on median OS. Thirty-two patients were vaccinated once with recombinant vaccinia containing the transgenes for prostate-specific antigen (PSA) and three costimulatory molecules. Patients received boosters with recombinant fowlpox containing the same four transgenes. Twelve of 32 patients showed declines in serum PSA post-vaccination and 2/12 showed decreases in index lesions. Median OS was 26.6 months (predicted median OS by the Halabi nomogram was 17.4 months). Patients with greater PSA-specific T-cell responses showed a trend (p = 0.055) toward enhanced survival. There was no difference in T-cell responses or survival in cohorts of patients receiving GM-CSF versus no GM-CSF. Patients with a Halabi predicted survival of <18 months (median predicted 12.3 months) had an actual median OS of 14.6 months, while those with a Halabi predicted survival of ≥18 months (median predicted survival 20.9 months) will meet or exceed 37.3 months, with 12/15 patients living longer than predicted (p = 0.035). Treg suppressive function was shown to decrease following vaccine in patients surviving longer than predicted, and increase in patients surviving less than predicted. This hypothesis-generating study provides evidence that patients with more indolent mCRPC (Halabi predicted survival ≥18 months) may best benefit from vaccine therapy.

Keywords

Cancer vaccine Immunotherapy Prostate cancer Overall survival PSA–TRICOM PROSTVAC 

Supplementary material

262_2009_782_MOESM1_ESM.tif (106 kb)
Supplementary figure (TIF 106 kb)

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • James L. Gulley
    • 1
    • 2
  • Philip M. Arlen
    • 1
    • 2
  • Ravi A. Madan
    • 1
    • 2
  • Kwong-Yok Tsang
    • 1
  • Mary P. Pazdur
    • 1
  • Lisa Skarupa
    • 1
  • Jacquin L. Jones
    • 2
  • Diane J. Poole
    • 1
  • Jack P. Higgins
    • 1
  • James W. Hodge
    • 1
  • Vittore Cereda
    • 1
  • Matteo Vergati
    • 1
  • Seth M. Steinberg
    • 3
  • Susan Halabi
    • 4
  • Elizabeth Jones
    • 5
  • Clara Chen
    • 6
  • Howard Parnes
    • 7
  • John J. Wright
    • 8
  • William L. Dahut
    • 2
  • Jeffrey Schlom
    • 1
  1. 1.Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Medical Oncology Branch, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaUSA
  3. 3.Biostatistics and Data Management Section, National Cancer InstituteNational Institutes of HealthRockvilleUSA
  4. 4.Department of Biostatistics and BioinformaticsDuke University School of MedicineDurhamUSA
  5. 5.Department of Diagnostic Radiology, Clinical CenterNational Institutes of HealthBethesdaUSA
  6. 6.Department of Nuclear Medicine, Clinical CenterNational Institutes of HealthBethesdaUSA
  7. 7.Division of Cancer Prevention, National Cancer InstituteNational Institutes of HealthRockvilleUSA
  8. 8.Investigational Drug Branch, Cancer Therapy and Evaluation Program, National Cancer InstituteNational Institutes of HealthRockvilleUSA

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