Discussing Provenge With Patients With Prostate Cancer

Nick Mulcahy

May 03, 2010

May 3, 2010 — Clinicians are likely to be hearing from patients about sipuleucel-T (Provenge, Dendreon), the immunotherapy that has just been approved by the US Food and Drug Administration (FDA) for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

Media coverage has been widespread about both the approval and anticipation of the approval, with stories in or on the New York Times, Associated Press, NBC, CBS, CNN, and many other outlets.

Because of the news coverage and for other reasons, patient expectations might need to be dampened and some education provided, suggested Richard Greenberg, MD, chief of urologic oncology at Fox Chase Cancer Center in Philadelphia, Pennsylvania.

"It's not a home run," Dr. Greenberg told Medscape Oncology. "The median improvement in survival was about 4 months, compared with placebo. That's not insignificant, but it's not a big change in the treatment of metastatic prostate cancer."

The survival benefit with Provenge is not that much greater than that with the most frequently used treatment in this setting, docetaxel (Taxotere, Sanofi-Aventis), he pointed out. Docetaxel and prednisone provided a 2.4-month survival advantage, compared with mitoxantrone and prednisone, in men with mCRPC (N Engl J Med. 2004;351:1502-1512).

However, the survival benefit with Provenge comes with another advantage — less toxicity, Dr. Greenberg noted. "It's well tolerated."

Dr. Greenberg said that part of the hype surrounding Provenge comes from the ubiquity of prostate cancer. "It's hard to meet someone who doesn't have prostate cancer in their family."

The fact that Provenge has long been referred to as a "vaccine" might contribute to the excitement — and potentially the confusion — about the new agent, he said.

"Patients may think that Provenge is like a vaccine for polio," said Dr. Greenberg

It's really not a vaccine. It's an immunotherapy.

"It's not preventative or a cure — that must be communicated to patients," he said. "It's really not a vaccine. It's an immunotherapy," he added.

Another important point is that Provenge is only for men with metastatic disease who have progressed on hormonal therapy and, among those men, only those with asymptomatic or minimally symptomatic disease, said Dr. Greenberg.

The best candidates for treatment are "appropriately selected" men — those with "good performance status" and a "low volume of bone involvement," he explained. "Those are the patients who do best with this treatment."

"Not every patient with metastatic castration-resistant prostate cancer needs to be on Provenge," he pointed out.

Dr. Greenberg believes that combination therapy with Provenge is likely. "I would imagine that Provenge will be used with chemotherapy agents in a multimodal approach in the future," he said.

"If we are to get a major improvement in overall survival, it will be with a multimodal approach," he said, not referring to Provenge specifically.

Only 2000 Men to Be Treated in First Year

The importance of using Provenge in appropriately selected men is partly related to the cost of the agent, said Dr. Greenberg.

Investment firm J.P. Morgan estimates that a full course of Provenge will cost $65,000; estimates by other analysts range from $50,000 to $100,000, according to report from CNN.

It's a lot of money, said Dr. Greenberg, but comparable to the cost of using bevacizumab and other targeted therapies in a variety of advanced cancers.

Money issues aside, Provenge will not be available to many men in the next year, according to the company Web site.

The manufacturer, Dendreon, reports that the therapy will be available through approximately 50 centers, all of which were approved clinical trial sites.

However, only 2000 men will be able to be treated in the first year.

The limitation is rooted in the manufacturing requirements for the autologous cellular immunotherapy, according to company materials.

On day 1 of the manufacturing process, a patient has blood drawn at a clinic, and autologous antigen-presenting cells are obtained from the patient using a standard leukapheresis procedure. The antigen-presenting cells are then couriered to the manufacturing facility.

On day 2 or 3, the antigen-presenting cells are cocultured with a recombinant fusion protein containing prostatic acid phosphatase, and the resulting Provenge is then couriered back to the clinic.

On day 3 or 4, the patient is infused with the therapy, which "can potentially stimulate a T cell response against prostate cancer cells," according to the company.

A complete course consists of 3 cycles of treatment that occur within 1 month.

Although manufacturing capabilities are currently limited, the company expects to increase capacity over the next year. The increased capacity will be the result of the anticipated licensure of facilities in New Jersey, Georgia, and California in mid-2011.

Immunotherapy for Cancer Works

The most notable advance with Provenge may be the use of an immunotherapy for cancer, Dr. Greenberg suggested. "It's a very different way to look at treating prostate cancer," he said.

Philip Kantoff, MD, a Provenge investigator, said in a press statement that the therapy is "the first of what we expect to be many more cancer immunotherapies in the future."

Our study provides proof that such an approach can work.

"For more than 20 years, scientists have been working on harnessing the immune system in a way that has beneficial effects for cancer patients, notably the prolongation of survival," said Dr. Kantoff, who is chief of the Division of Solid Tumor Oncology and chief clinical research officer at Dana-Farber Cancer Institute in Boston, Massachusetts. "Our study provides proof that such an approach can work."

Other companies are following Dendreon's lead in prostate cancer.

Days before Provenge was approved, Bavarian Nordic of Denmark announced that its prostate-specific antigen–targeted poxviral vaccine (Prostvac) was granted fast-track designation by the FDA for its proposed use in the treatment of men with asymptomatic or minimally symptomatic mCRPC.

The investigational therapy met FDA criteria for the designation because it demonstrated "a potential survival benefit and an excellent safety profile" in a randomized, placebo-controlled phase 2 trial with 122 men with mCRPC, according to a company press statement.

Provenge Clinical Details

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

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.

This 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.

Dr. Greenberg and Dr. Kantoff have disclosed no relevant financial relationships.