Provenge Fares OK at CMS Review

Confidence about vaccine evidence not high

Nick Mulcahy

November 18, 2010

November 18, 2010 — The prostate cancer vaccine sipuleucel-T (Provenge, Dendreon) received a middling vote of confidence for its on-label use and what amounted to a thumbs-down vote for its off-label use at a meeting of the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) on November 17.

The meeting is part of a national coverage analysis of Provenge by the Centers for Medicare and Medicaid Services (CMS).

The novel vaccine was approved by the US Food and Drug Administration (FDA) earlier this year for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer.

In the pivotal phase 3 study, there was a 4.1-month median survival advantage with Provenge, compared with placebo.

The analysis by CMS has garnered a great deal of attention for a variety of reasons, including the fact that the therapy costs a reported $93,000.

The analysis will be completed by June 30, 2011, and might be used when determining Medicare coverage of Provenge, according to an industry newsletter, The Pink Sheet.

MEDCAC reviewed Provenge data and voted on 5 key questions about the therapy. The questions required that committee members indicate their confidence in evidence regarding efficacy (survival, disease-related symptoms) and other matters on a scale of 1 to 5 (1 being low and 5 being high).

The committee averaged a final vote of 3.6 on the question of their confidence in the evidence that Provenge significantly improves overall survival in patients.

"It's clear that they believe from their voting that there is a survival benefit," said Daniel Petrylak, MD, one of the Provenge investigators and codirector of the Prostate Cancer Program at the Columbia University Medical Center in New York City. Dr. Petrylak attended the meeting and spoke for 5 minutes during the scheduled public comment period. He spoke with Medscape Medical News afterward.

The committee did not cast a final vote on their confidence in Provenge's ability to improve disease symptoms because the preliminary vote on the matter was not high enough to cast a second and final vote.

The committee averaged a final vote of 3.1 on the question of their confidence in the evidence that Provenge significantly improves the avoidance of the treatment burdens (e.g., access, delivery, and adverse effects) associated with anticancer therapy in these patients.

The vote on the possibility of off-label use was not encouraging. The committee averaged a final vote of 1.1 to 1.4 on the questions of whether conclusions about Provenge are generalizable to unlabeled use in 3 different types of patients not included in the FDA's indication — including patients whose disease has not metastasized.

The committee saved its highest vote (4.1) for the question of their confidence in conclusions about Provenge being generalizable to community-based settings.

Another Moderate Endorsement

The MEDCAC meeting and voting come on the heels of a report issued by the Agency for Health Research and Quality (AHRQ) that analyzed outcomes with the novel therapy; the report is also part of the CMS's review process.

The report authors, much like MEDCAC, conclude that they have "moderate confidence that the evidence reflects the true effect" of treatment. The report called into question the exact length of survival benefit seen with Provenge because the therapy was tested in conjunction with postprogression chemotherapy.

"The current existing analyses are insufficient to know to what degree sipuleucel-T is effective in the absence of chemotherapy or [to what degree it] depends on chemotherapy to demonstrate improvement in survival," according to the report, which was commissioned by AHRQ and written by the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-Based Practice Center in Chicago, Illinois.

However, Dr. Petrylak perceived the matter differently. "I published a study at [the 2010 annual meeting of the American Society of Clinical Oncology] that survival was independent of docetaxel [both] pre- [and] post-Provenge," he said.

The MEDCAC meeting comes at a time in which exorbitant price tags for cancer therapies that offer modest survival benefit are being questioned.

However, when the Provenge survival data were first presented at the 2009 annual meeting of the American Urological Association (AUA), one the investigators hailed the survival benefit as something more than modest.

"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.

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