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

Published

Journal Article

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 > or =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 > or =18 months) may best benefit from vaccine therapy.

Full Text

Duke Authors

Cited Authors

  • Gulley, JL; Arlen, PM; Madan, RA; Tsang, K-Y; Pazdur, MP; Skarupa, L; Jones, JL; Poole, DJ; Higgins, JP; Hodge, JW; Cereda, V; Vergati, M; Steinberg, SM; Halabi, S; Jones, E; Chen, C; Parnes, H; Wright, JJ; Dahut, WL; Schlom, J

Published Date

  • May 2010

Published In

Volume / Issue

  • 59 / 5

Start / End Page

  • 663 - 674

PubMed ID

  • 19890632

Pubmed Central ID

  • 19890632

Electronic International Standard Serial Number (EISSN)

  • 1432-0851

Digital Object Identifier (DOI)

  • 10.1007/s00262-009-0782-8

Language

  • eng

Conference Location

  • Germany