Results of a milestone study on the use of an experimental form of immunotherapy may usher in a new era in the management of androgen-independent prostate cancer.
As reported at the AUA annual meeting here, sipuleucel-T significantly improved survival in men with advanced prostate cancer in a pivotal phase III trial.
Data from the Immunotherapy for Prostate AdenoCarcinoma Treatment (IMPACT) study showed that, compared to placebo, sipuleucel-T extended median survival by 4.1 months (25.8 vs. 21.7 months) and improved 3-year survival by 38% (31.7% vs. 23%). The agent reduced the overall risk of death by 22.5% compared to placebo (p=.032), exceeding the pre-specified level of statistical significance defined by the study's design (<.043).
Sipuleucel-T exhibited a favorable safety profile consistent with prior trials of the agent, a fact that researchers said would give the agent an important advantage over chemotherapy.
A total of 512 patients were enrolled in the IMPACT trial, a multicenter, randomized, double-blind, placebo-controlled study evaluating men with asymptomatic or minimally symptomatic, metastatic, androgen-independent prostate cancer. The primary endpoint was overall survival.
New treatment paradigm
"The results from this landmark study confirm that Provenge prolongs survival with a favorable benefit-to-risk profile," said Paul Schellhammer, MD, professor of urology at Eastern Virginia Medical School, Norfolk, and a principal investigator of the IMPACT study. "The treatment effect on overall survival was clinically meaningful, robust, and consistent across subpopulations, and the effect on long-term survival was particularly impressive.
"If approved, Provenge has the potential to fill a large unmet medical need and create a new paradigm using immunotherapy for the treatment of men with advanced prostate cancer."
The treatment effect of sipuleucel-T was consistent across a number of patient subsets and remained consistent using the log rank test and an unadjusted Cox model (HR=0.766, p=.023) and after adjustment for docetaxel (Taxotere) use following investigational therapy (HR=0.763; p=.036). (The crossover design of the study allowed patients in both the treatment and placebo arms to receive docetaxel; about half of the patients in each arm received docetaxel, which is currently the only FDA-approved treatment for hormone-refractory prostate cancer.)
"What's impressed me about these data is they're incredibly consistent," said David Penson, MD, MPH, associate professor of urology at the University of Southern California, Los Angeles, who presented the IMPACT data at the AUA meeting. "The story is exactly the same and the direction is right in every single subgroup analysis. And that is very reassuring to me."
Prostate cancer-specific survival also favored the sipuleucel-T arm of the study (HR=0.772; p=.036). Sipuleucel-T did not significantly delay time to progression, consistent with other trials in this patient population.
Favorable side effect profile
Dr. Penson, who is an IMPACT site investigator, said the most common adverse events associated with sipuleucel-T (those occurring in more than 5% of patients) were chills, pyrexia, and headache-similar to events seen in previous trials. Adverse events were generally low grade with a short duration (1 to 2 days).
"When you give these patients the Provenge product, they often have sort of a watered-down transfusion reaction," Dr. Penson said. "It goes away within 24 hours."
Nearly all patients (99%) were able to tolerate all three monthly treatment cycles, he pointed out.
"I was always very impressed by how well this drug is tolerated," Dr. Penson said. "A number of my patients will get the drug on Friday and then go play golf on Saturday. That's not an exaggeration. These patients really tolerate this agent very nicely."
The drug requires patients to undergo apheresis, but administering the drug itself is performed on an outpatient basis.
"You have to be able to infuse IV fluids to give this agent," Dr. Penson said. "Having said that, it could be given in any doctor's office that has an IV pole, some basic vital sign monitoring equipment, and a nurse who can put in an IV needle.
"What I would say to my urologic colleagues is, this is no different from intravesical BCG, which we give for superficial bladder cancer. In fact, that agent probably has more side effects than this one. I really hope urologists will give it. I know they can."