Marie L. Huber, Laura Haynes, Chris Parker, Peter Iversen
Manuscript received July 11, 2011; revised November 7, 2011; accepted November 16, 2011.
Correspondence to: Marie L. Huber, MPhil, PO Box 925, New York, NY 10009 (e-mail: firstname.lastname@example.org).
Sipuleucel-T was approved by the US Food and Drug Administration on April 29, 2010, as an immunotherapy for late-stage pros-tate cancer. To manufacture sipuleucel-T, mononuclear cells harvested from the patient are incubated with a recombinant prostatic acid phosphatase (PAP) antigen and reinfused. The manufacturer proposes that antigen-presenting cells exogenously activated by PAP induce endogenous T-cells to attack PAP-bearing prostate cancer cells. However, the lack of demonstrable tumor responses has prompted calls for scrutiny of the design of the trials in which sipuleucel-T demonstrated a 4-month survival ben-efit. Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be prognostic for survival in castration-resistant prostate cancer patients receiving chemotherapy. Because two-thirds of the cells harvested from placebo patients, but not from the sipuleucel-T arm, were frozen and not reinfused, a detrimental effect of this large repeated cell loss provides a potential alternative explana-tion for the survival “benefit.” Patient safety depends on adequately addressing this alternative explanation for the trial results.
J Natl Cancer Inst 2012;104:273–279