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

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.

• Authors: 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
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 59 Issue 5 Pg. 663-74 (May 2010) ISSN: 1432-0851 [Electronic] Germany
• PMID: 19890632 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Androgen Antagonists
• Antigens, Neoplasm
• Antineoplastic Agents
• Cancer Vaccines
• Taxoids
• Docetaxel
• Granulocyte-Macrophage Colony-Stimulating Factor
• Prostate-Specific Antigen

Topics

• Aged
• Androgen Antagonists (therapeutic use)
• Antigens, Neoplasm (immunology, therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Cancer Vaccines (immunology, therapeutic use)
• Docetaxel
• Granulocyte-Macrophage Colony-Stimulating Factor (immunology, therapeutic use)
• Humans
• Kaplan-Meier Estimate
• Male
• Poxviridae (genetics)
• Prognosis
• Prostate-Specific Antigen (genetics, immunology)
• Prostatic Neoplasms (immunology, pathology, therapy)
• Taxoids (therapeutic use)
• Transgenes