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

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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.

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Acknowledgments

Grant support: Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health. The authors thank Bonnie L. Casey and Debra Weingarten for their editorial assistance in the preparation of the manuscript.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, Bethesda, MD, 20892, USA

    James L. Gulley, Philip M. Arlen, Ravi A. Madan, Kwong-Yok Tsang, Mary P. Pazdur, Lisa Skarupa, Diane J. Poole, Jack P. Higgins, James W. Hodge, Vittore Cereda, Matteo Vergati & Jeffrey Schlom

  2. Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 13N240E, Bethesda, MD, 20892, USA

    James L. Gulley, Philip M. Arlen, Ravi A. Madan, Jacquin L. Jones & William L. Dahut

  3. Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, 6116 Executive Boulevard, Room 702, Rockville, MD, 20852, USA

    Seth M. Steinberg

  4. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Box 2721, DUMC, Durham, NC, 27710, USA

    Susan Halabi

  5. Department of Diagnostic Radiology, Clinical Center, National Institutes of Health, 10 Center Drive, Room 1C372, Bethesda, MD, 20892, USA

    Elizabeth Jones

  6. Department of Nuclear Medicine, Clinical Center, National Institutes of Health, 10 Center Drive, Room 1C401, Bethesda, MD, 20892, USA

    Clara Chen

  7. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, 6130 Executive Blvd, Room 2100, Rockville, MD, 20852, USA

    Howard Parnes

  8. Investigational Drug Branch, Cancer Therapy and Evaluation Program, National Cancer Institute, National Institutes of Health, 6130 Executive Blvd, Room 7122, Rockville, MD, 20852, USA

    John J. Wright

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  1. James L. Gulley
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Correspondence to Jeffrey Schlom.

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Gulley, J.L., Arlen, P.M., Madan, R.A. et al. Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother 59, 663–674 (2010). https://doi.org/10.1007/s00262-009-0782-8

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