title: 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.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.forename: Kwong-Yok
authors.initials: KY
authors.lastname: Tsang
authors.forename: Mary P
authors.initials: MP
authors.lastname: Pazdur
authors.forename: Lisa
authors.initials: L
authors.lastname: Skarupa
authors.forename: Jacquin L
authors.initials: JL
authors.lastname: Jones
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Poole
authors.forename: Jack P
authors.initials: JP
authors.lastname: Higgins
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
authors.forename: Vittore
authors.initials: V
authors.lastname: Cereda
authors.forename: Matteo
authors.initials: M
authors.lastname: Vergati
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jones
authors.forename: Clara
authors.initials: C
authors.lastname: Chen
authors.forename: Howard
authors.initials: H
authors.lastname: Parnes
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D000077143:Docetaxel; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D011212:Poxviridae / Q000235:genetics; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D043823:Taxoids / Q000627:therapeutic use; D019076:Transgenes
chemical_list: D000726:Androgen Antagonists; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D043823:Taxoids; D000077143:Docetaxel; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017430:Prostate-Specific Antigen