C129
Analysis of factors influencing survival in patients with metastatic hormone-refractory prostate cancer (mHRPC) following GVAX immunotherapy for prostate cancer
David Smith1, Eric Small2, John Corman3, Celestia Higano4, Minh Nguyen5, Thomas Harding5, Karin Jooss5, Dimitrios Chondros5
1University of Michigan, Ann Arbor, MI, USA, 2University of California, San Francisco, CA, USA, 3Virginia Mason Medical Center, Seattle, WA, USA, 4University of Washington, Seattle, WA, USA, 5Cell Genesys Inc., South San Francisco, CA, USA
Background
GVAX immunotherapy for prostate cancer is comprised of two allogeneic prostate carcinoma cell lines modified to secrete GM-CSF. This immunotherapy showed encouraging survival in two multicenter, phase 2 studies in patients with mHRPC. Analyses were undertaken to explore factors potentially associated with survival.
Method
Chemotherapy-naïve patients with mHRPC received immunotherapy for 24 weeks. Predicted survival was calculated based on a validated prognostic model and compared to observed survival (Kaplan-Meier Method) from the two studies. Antibody (Ab) responses to specific antigens were evaluated from one study (n=65) for association with survival using the Cox regression model, adjusted for prognostic factors and dose groups.
Results
Observed median survival (34.9 months and 35.0 months) exceeded the predicted survival (22.5 months and 22.0 months) in patients receiving the higher doses in each trial. Antibody induction against HLA-A24 and FLJ14668 was associated with longer survival (p=0.05 and p=0.002, respectively), independent of dose and number of administrations.
Conclusions
Survival data from two phase 2 immunotherapy studies show consistent results in patients with mHRPC, which compare favorably to predicted survival based on known prognostic factors and to results reported in chemotherapy studies. An immune response to specific antigens was associated with improved survival, which supports further identification of candidate biomarkers that will be examined in the currently ongoing phase 3 studies. VITAL-2, one of the phase 3 studies, is currently enrolling patients with symptomatic mHRPC. Patients are randomized to docetaxel and immunotherapy or docetaxel with prednisone; the primary endpoint is survival.
