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- Title
Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer.
- Authors
Gulley, James L; Arlen, Philip M; Madan, Ravi A; Tsang, Kwong-Yok; Pazdur, Mary P; Skarupa, Lisa; Jones, Jacquin L; Poole, Diane J; Higgins, Jack P; Hodge, James W; Cereda, Vittore; Vergati, Matteo; Steinberg, Seth M; Halabi, Susan; Jones, Elizabeth; Chen, Clara; Parnes, Howard; Wright, John J; Dahut, William L; Schlom, Jeffrey
- 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 > 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.
- Publication
Cancer immunology, immunotherapy : CII, 2010, Vol 59, Issue 5, p663
- ISSN
1432-0851
- Publication type
Journal Article
- DOI
10.1007/s00262-009-0782-8