CHICAGO — Autologous active cellular immunotherapy with sipuleucel-T, the controversial investigative agent with the brand name Provenge, extended survival by a median of 4.1 months in men with metastatic androgen-independent prostate cancer, according to the most recent data from the IMPACT study.
The much-anticipated results of the phase III, multicenter, randomized, double-blind, placebo-controlled trial were presented in a late-breaking science forum at the annual meeting of the American Urological Association.
“The data show that sipuleucel-T is the first active immunotherapy to demonstrate an improvement in overall survival for advanced prostate cancer,” said coinvestigator Dr. David F. Penson of the University of Southern California in Los Angeles.
“Provenge appears to have a highly favorable benefit-to-risk profile [and] a short duration of therapy, and perhaps most importantly, will not only change the way we manage prostate cancer, but also has the potential to create an entirely novel therapeutic paradigm across the field of oncology,” he said.
Median survival reached 25.8 months with treatment and 21.7 months with placebo. The 3-year survival rate was 31.7% with treatment and 23% with placebo, a relative increase of 38% (P = .032). The hazard ratio was 0.775, indicating a 22.5% reduction in the risk of death in the sipuleucel-T treatment arm.
The experimental vaccine from Dendreon Corp. still had not met the primary end point when interim results from the IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) trial were made public in fall 2008. An earlier Food and Drug Administration decision not to approve Provenge, pending more data, had triggered demonstrations by patient advocates of the therapy.
The IMPACT trial included 512 patients with minimally symptomatic or asymptomatic advanced androgen-independent prostatic adenocarcinoma with metastasis to lymph nodes or bone, who had a life expectancy of at least 6 months and a serum prostate-specific antigen (PSA) level greater than 5 ng/mL. They were randomized at a 2:1 ratio to receive the experimental vaccine or a placebo. In all, 90% of patients completed treatment.
The active cellular immunotherapy is designed to stimulate and optimize production of the patient's T cells and to enlist these cells in the destruction of specific tumor cell types.
At the time of disease progression, patients in both arms of the study were able to receive treatment at the physician's discretion. Patients who were randomized to placebo had the option of receiving immunotherapy in which they received a version of sipuleucel-T prepared from their own cryopreserved cells, which had been harvested at the time of placebo generation. Patients randomized to sipuleucel-T had the option of receiving an additional dose of docetaxel (Taxotere).
The investigational therapy produced only minor—in most cases, transitory—side effects, Dr. Penson said.
This favorable safety profile makes the immunotherapy particularly promising as a treatment for patients with terminal prostate cancer because it preserves quality of life while prolonging life, he said.
The survival benefit found with sipuleucel-T in this study has major significance for patients with advanced prostate cancer, he said. “When you consider that these patients have less than a 2-year survival advantage on average, and you're going to give them 4 more months of life, that's a 20% advantage.”
To rule out the possibility of the survival benefit being driven by a particular group of patients, the treatment effect was assessed in multiple population subsets. All subpopulations demonstrated a positive treatment effect, Dr. Penson reported.
The survival benefit of sipuleucel-T shown in this study is consistent with two earlier multicenter, randomized, double-blind, placebo-controlled trials of the agent, Dr. Penson said. An integrated analysis of the three studies, which includes a total of 737 patients, reveals a hazard ratio of 0.735, which represents a 26.5% reduction in the risk of death, with a P value of less than .001, he said.
Dr. Penson said that he had no disclosures related to the study.