Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer.
BACKGROUND
Sipuleucel-T is an investigational active cellular immunotherapy product designed to stimulate an immune response against prostate cancer. The safety and efficacy of sipuleucel-T was evaluated in 2 identically designed, randomized, double-blind, placebo-controlled trials (D9901 and D9902A) conducted in men with advanced prostate cancer.


METHODS
A total of 225 patients were randomized in D9901 or D9902A to sipuleucel-T (n = 147) or placebo (n = 78), given as 3 intravenous infusions approximately 2 weeks apart. Patients were followed for survival until death or a prespecified cutoff of 36 months after randomization.


RESULTS
In the integrated analysis of D9901 and D9902A, patients randomized to sipuleucel-T demonstrated a 33% reduction in the risk of death (hazard ratio, 1.50; 95% confidence interval, 1.10-2.05; P = .011; log-rank). The treatment effect remained strong after performing adjustments for imbalances in baseline prognostic factors, poststudy treatment chemotherapy use, and non-prostate cancer-related deaths. Additional support for the activity of sipuleucel-T is provided by the correlation between a measure of the product's potency, CD54 up-regulation, and overall survival. The most common adverse events associated with treatment were chills, pyrexia, headache, asthenia, dyspnea, vomiting, and tremor. These events were primarily grade 1 and 2, with durations of 1 to 2 days.


CONCLUSIONS
The integrated results of D9901 and D9902A demonstrate a survival benefit for patients treated with sipuleucel-T compared with those treated with placebo. The generally modest toxicity profile, coupled with the survival benefit, suggests a favorable risk-benefit ratio for sipuleucel-T in patients with advanced prostate cancer.
Higano
Celestia S
CS
Department of Oncology and Urology, University of Washington, Seattle, WA, USA. thigano@u.washington.edu
Schellhammer
Paul F
PF
Small
Eric J
EJ
Burch
Patrick A
PA
Nemunaitis
John
J
Yuh
Lianng
L
Provost
Nicole
N
Frohlich
Mark W
MW
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D007110:Immunity, Active; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010919:Placebos; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use*
D019496:Cancer Vaccines; D010919:Placebos; D014020:Tissue Extracts; C511774:sipuleucel-T