FDA Requests More Data for Prostate Cancer Vaccine

Norra MacReady

May 23, 2007

May 23, 2007 (Anaheim) — The US Food and Drug Administration (FDA)'s request for more data before approving a prostate cancer vaccine was a blow to many doctors and patients who were anticipating its arrival, David F. Penson, MD, said yesterday at the annual meeting of the American Urological Association.

“I personally am disappointed by the FDA’s decision,” said Dr. Penson, an investigator in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) study, an ongoing phase 3 clinical trial of the vaccine.

Sipuleucel-T, usually referred to by its brand name, Provenge, is supposed to enhance a patient’s response to chemotherapy by stimulating T-cell response to prostatic acid phosphatase. Dendreon, the Seattle, Washington company that makes the vaccine, is planning to market it only to men with advanced androgen-independent prostate cancer.

In a phase 3 study published last year (Small et al. J Clin Oncol. 2006;24:3089-94), the vaccine failed to meet its primary endpoint: a significant increase in time to disease progression (TTP) in men with asymptomatic prostate cancer. The 82 patients who received the vaccine had a median TTP of 10 weeks, compared with 11.7 weeks for the placebo group, a finding that just missed statistical significance (P = .052). However, median survival among the men who got the vaccine was 25.9 months, compared with 21.4 months for the placebo group (P = .01). The authors concluded that sipuleucel-T is well tolerated and might confer a survival advantage, even though the improvement in the primary endpoint was not statistically significant.

In general, median survival in this patient population is 18 to 21 months, so “a 4.5-month increase in survival is very significant to these patients,” said Dr. Penson, who was not involved in that study. However, he noted, many of the IMPACT subjects in his trial know when they are in the treatment group because they feel so much better. He also pointed out that the FDA’s 17-member Oncology Drugs Advisory Committee (ODAC) voted unanimously to declare the vaccine safe, and 13 agreed that it met the criteria for efficacy or evidence of benefit necessary for approval. Dr. Penson, an associate professor of urology at the Keck School of Medicine, University of Southern California, Los Angeles, confessed to being mystified why the FDA overruled the recommendation of its own committee in favor of asking for more data.

One factor might have been a letter that the FDA received shortly after the ODAC’s votes were cast. In its April 13 issue, The Cancer Letter, an oncology newsletter, published the missive, written by ODAC member Howard Scher, MD, chief of the genitourinary oncology service at Memorial Sloan-Kettering Cancer Center in New York City. Referring to the 2006 study and to a study that was aborted in 2002 after data analysis showed no significant improvement in TTP associated with this agent, Dr. Scher noted that since neither of these trials met their primary endpoints, their data must be considered “exploratory” and “hypothesis gathering.” Any survival difference might have occurred by chance. Also lacking were data on an antitumor effect, as measured by parameters such as prostate-specific antigen, regression or stabilization of soft-tissue or bony metastases, quality of life, and pain. He urged the FDA to delay any approval decision until the IMPACT study has been completed and analyzed. ODAC chair Maha Hussain, MD, professor of medicine and urology at the University of Michigan, in Ann Arbor, also voted against approving the drug until more data are in.

IMPACT will stop enrollment by the end of 2007, and an interim analysis is scheduled for 2008. It is possible the FDA will approve the vaccine then, but most likely it will wait until the final analysis appears, which will not be until 2010, Dr. Penson said.

In the meantime, “these men are desperate — they are lining up to be in a study, because they can’t get the drug commercially,” he noted.

AUA 2007 Annual Meeting: News briefing on prostate cancer vaccine. Presented May 21, 2007.

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