940P - Overall survival benefit with sipuleucel-T by baseline prostate-specific antigen (PSA): an exploratory analysis from three phase 3 trials

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Prostate Cancer
Cancer Immunology and Immunotherapy
Presenter Philip Kantoff
Authors P. Kantoff1, G. Chodak2, R. Sims3, J.B. Whitmore4, P. Schellhammer5
  • 1Medical Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 2Oncology, Weiss Memorial Hospital, Chicago/US
  • 3Clinical Affairs, Dendreon Corporation, Seattle/US
  • 4Biometrics, Dendreon, 92101 - Seattle/US
  • 5Urology, Eastern Virginia Medical School / Urology of Virginia, Virginia/US

Abstract

Introduction and objective

Sipuleucel-T is an autologous cellular immunotherapy approved for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC) based on improved overall survival (OS) in the pivotal phase 3 IMPACT trial (NCT00065442). In a subgroup analysis of pooled data from three Phase 3 trials of sipuleucel-T in mCRPC, baseline PSA was found to be the most significant predictive factor for OS. To further investigate the impact of baseline PSA levels on outcomes following sipuleucel-T, we conducted an exploratory analysis of patients (pts) from three Phase 3 trials.

Methods

The analysis included all 737 randomized pts from three Phase 3 trials (D9901, D9902A and IMPACT). Pts were categorized by baseline PSA quartile (Table), as well as by ECOG PS, and median for other baseline prognostic variables (i.e. lactate dehydrogenase [LDH], alkaline phosphatase [ALP], and hemoglobin [Hgb]). Median OS and hazard ratio (HR) were estimated using Kaplan-Meier and Cox models, respectively.

Results

HR values suggest consistent treatment effect in all subsets, although there is inadequate power to show statistical significance within each quartile. There was a trend toward an increased magnitude of treatment benefit in pts with a lower baseline PSA (Table). Results for other baseline prognostic variables also suggest a trend toward greater benefit with better prognostic features. However, results for baseline Hgb indicated an opposite trend

Conclusions

Although not powered for statistical significance, this analysis supports a consistent OS benefit with sipuleucel-T across PSA quartiles in patients enrolled in Phase 3 trials. The greater benefit with lower baseline PSA suggests that pts with less advanced disease may benefit more from sipuleucel-T.

Baseline PSA (ng/mL)
≤22.3 >22.3– ≤ 49.9 >49.9– ≤ 137.8 >137.8
n 184 184 184 183
Median OS, mos
Sipuleucel-T 41.2 25.9 20.6 15.1
Control 26.7 22.0 14.8 13.5
Difference 14.5 3.9 5.8 1.6
HR; 95% CI 0.48; 0.32–0.73 0.76; 0.53–1.11 0.67; 0.47–0.95 0.88; 0.62–1.25

Disclosure

P. Kantoff: Advisory boards for Dendreon Corporation

G. Chodak: Stock ownership in Amgen; Advisory boards for Dendreon Corporation and Janssen; Honoraria for Dendreon Corporation and Amgen.

R.B. Sims: Stock ownership and employee of Dendreon Corporation.

J.B. Whitmore: Employee of Dendreon Corporation; Stock ownership in Dendreon Corporation and Amgen,

P. Schellhammer: Honoraria for Dendreon Corporation