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Updated Survival Results of the IMPACT Trial of Sipuleucel-T for Metastatic Castration-Resistant Prostate Cancer
E. Roy Berger, MD1, Philip W. Kantoff, MD2, Celestia S. Higano, MD3, Neal D. Shore, MD4, Eric J. Small, MD5, David F. Penson, MD6, Robert B. Sims, MD7, Yi Xu, PhD7, Mark W. Frohlich, MD7, Paul F. Schellhammer, MD8.
1SUNY School of Medicine, Stony Brook, NY, USA, 2Harvard Medical School, Boston, MA, USA, 3University of Washington, Seattle, WA, USA, 4Grand Strand Urology, Myrtle Beach, SC, USA, 5UCSF Urologic Oncology Program, San Francisco, CA, USA, 6Vanderbilt University Medical Center, Nashville, TN, USA, 7Dendreon Corporation, Seattle, WA, USA, 8Eastern Virginia Medical School, Norfolk, VA, USA.

BACKGROUND: Sipuleucel-T is an investigational autologous active cellular immunotherapy for the treatment of prostate cancer. The IMPACT study (IMmunotherapy Prostate AdenoCarcinoma Treatment), a randomized, double-blind, placebo controlled Phase 3 trial in asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (CRPC) demonstrated a significant prolongation of overall survival (OS). Supplemental analyses, including OS based on additional events collected prior to study closure, are reported.
METHODS: 512 patients were randomized (2:1) to receive 3 intravenous doses of sipuleucel-T (n=341) or placebo (n=171) in the outpatient setting at 2-week intervals. Patients were stratified by primary Gleason grade, number of bone metastases, and bisphosphonate use. OS was analyzed with a stratified Cox regression model adjusted for baseline prostate-specific antigen (PSA) and lactate dehydrogenase (LDH; primary model), and with an unadjusted stratified Cox model and the log rank test. The median survival time and survival probabilities were estimated using the Kaplan-Meier method.
RESULTS: Prognostic factors were well-balanced; the median predicted OS of patients in the sipuleucel-T and placebo arms was 20.3 and 21.2 months, respectively, using the Halabi model. At the time of data cutoff (331 death events), OS was significantly prolonged for sipuleucel-T patients (hazard ratio [HR]=0.775; P=0.032). Results were consistent in multiple patient subgroups. The sipuleucel-T survival effect remained significant when patients were censored at time of first docetaxel use (HR=0.649; P=0.009) and when post-randomization docetaxel was treated as a time dependent covariate (HR=0.777; P=0.034). In the updated analysis at the time of study closure (349 death events), the estimated median follow-up time was 36.5 months. The sipuleucel-T treatment effect remained significant using the primary model (HR=0.759; P=0.017) or unadjusted Cox model and log rank test (HR=0.751; P=0.012). Unchanged was the median survival of 25.8 and 21.7 months. Survival probability at 36 months was 32.1% and 23.0% in the sipuleucel-T and placebo arms, respectively. Adverse events observed in ≥ 5% of patients randomized to sipuleucel-T and observed at least twice as frequently in the sipuleucel-T arm included chills, pyrexia, headache, influenza-like illness, myalgia, hypertension, and hyperhidrosis. The majority of these events were Grade 1 or 2 in severity, occurred within 1 day after infusion, and resolved within 1-2 days.
CONCLUSIONS: Additional analyses confirm the improved OS findings previously reported for sipuleucel-T in metastatic CRPC.


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