FDA Approves Provenge, the First Immunotherapy for Metastatic Prostate Cancer

Nick Mulcahy

April 29, 2010

April 29, 2010 — In a widely anticipated announcement, the US Food and Drug Administration (FDA) has approved an immunotherapy, sipuleucel-T (Provenge, Dendreon), for the treatment of asymptomatic or minimally symptomatic metastatic, castration-resistant prostate cancer (mCRPC).

Often referred to as a vaccine, sipuleucel-T is an autologous active cellular immunotherapy, meaning that it is made from the patient's own white blood cells and stimulates a patient's immune system to respond against the cancer. The treatment needs to be manufactured individually for each patient.

"The availability of [sipuleucel-T] provides a new treatment option for men with advanced prostate cancer who currently have limited effective therapies available," said Karen Midthun, MD, acting director of the FDA's Center for Biologics Evaluation and Research, in a press statement.

Sipuleucel-T becomes the first product approved by the FDA in a new therapeutic class known as active cellular immunotherapies, according to Dendreon press materials.

To be approved by the FDA, investigators had to show that sipuleucel-T would extend survival in men with mCRPC.

In the pivotal phase 3 study, with a median follow-up of 36.5 months, men treated with sipuleucel-T (n = 341) had a median survival of 25.8 months, compared with men treated with placebo (n = 171), who had a median survival of 21.7 months

Thus, with the new therapy, there was a 4.1-month median survival advantage and a 24.1% reduction in the risk for death (hazard ratio, 0.759; P = .017), compared with placebo.

These latest data from the pivotal trial, known as IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment), were presented at the American Society of Clinical Oncology 2010 Genitourinary Cancers Symposium in March.

Last year, after a presentation of very similar survival data on sipuleucel-T at the 2009 American Urological Association (AUA) annual meeting, one of the study investigators hailed the survival benefit.

This 4-month extension in survival is very, very significant.

"This 4-month extension in survival is very, very significant," said David F. Penson, MD, MPH, at the AUA meeting. Dr. Penson is a professor of medicine at the University of Southern California Los Angeles.

"These patients have a life expectancy of about 2 years, so giving them 4 more months is pretty important. It gives them about 20% more life. And [sipuleucel-T] does it with minimal adverse events. So there is improved survival with good quality of life," he added.

According to the FDA press release, the most common adverse reactions reported with the new product are chills, fatigue, fever, back pain, nausea, joint ache, and headache. The majority of adverse reactions were mild or moderate. Serious adverse reactions, which were reported in approximately one quarter of the patients receiving sipuleucel-T, included some acute infusion reactions and stroke.

Cerebrovascular events, including hemorrhagic and ischemic strokes, were observed in 3.5% of patients in the sipuleucel-T group, compared with 2.6% of patients in the placebo control group

The approval of sipuleucel-T has been a long time coming.

In 2007, the FDA deferred approval of sipuleucel-T until a statistically significant improvement in survival could be shown.

The study investigators revealed such an improvement at the 2009 AUA annual meeting.

We don't have anything for patients with hormone-refractory disease.

At the time, AUA spokesman J. Brantley Thrasher, MD, chair of the Department of Urology at the University of Kansas Medical Center in Kansas City, said that "this will cause a big splash."

"We don't have anything for patients with hormone-refractory disease, which is very aggressive. . . . Improved survival with T cell immunotherapy is really very significant," he said.

Dr. Penson and Dr. Thrasher previously disclosed no relevant financial relationships.