Medicare Advisory Panel Reviews Data on Provenge
On November 17, a Medicare advisory panel offered moderately strong support for the prostate cancer immunotherapy drug sipuleucel-T (Provenge). The Medicare Evidence Development & Coverage Advisory Committee, or MEDCAC, generally agreed that the available data indicate the therapy is effective for its FDA-approved use: the treatment of men with metastatic prostate cancer who are experiencing few or no symptoms from the disease. The panel’s decision was part of a National Coverage Analysis (NCA) initiated earlier this year, which will determine whether Medicare will cover sipuleucel-T treatment for Medicare beneficiaries.
The FDA approved sipuleucel-T in April 2010. The approval was based on results from a phase III clinical trial called IMPACT, which showed that the treatment—called autologous cellular immunotherapy, because it uses a modified form of patients’ own white blood cells—improved median overall survival for men with metastatic hormone-refractory prostate cancer by 4.1 months compared with men who received a placebo treatment. The treatment also had little evidence of serious side effects.
The NCA was initiated, agency officials said, because of questions that had been raised about whether the therapy—which consists of three vaccinations over a 4- to 6-week period at a total cost of $93,000—would be covered by all of Medicare’s regional carriers.
The panel voted on a series of questions about the treatment using a rating system from 1 to 5, with 1 being a vote of low confidence and 5 representing a vote of high confidence. On the question of whether there was adequate evidence to support a survival improvement in men with asymptomatic/mildly symptomatic metastatic prostate cancer, the panel’s average score was 3.6. In addition, an independent technology assessment conducted by the Blue Cross & Blue Shield Technology Evaluation Center concluded that the evidence to support sipuleucel-T’s efficacy was “moderate.”
The committee had less confidence that the survival results with sipuleucel-T could be expected for so-called off-label indications, such as men with heavily symptomatic metastatic prostate cancer or nonmetastatic prostate cancer. The panel’s average score for that question was 1.2.
During the meeting’s public comment session, both medical professionals and patient advocates voiced strong support for sipuleucel-T. The only other treatment approved for metastatic hormone-refractory prostate cancer, the chemotherapy drug docetaxel, has significant toxicities that deter many men from taking it, several presenters noted. With sipuleucel-T, said Dr. Mark Scholz of Prostate Oncology Specialists in California, there is now “an effective treatment that can be administered to relatively frail patients without ruining their quality of life.”
During a committee debate, however, panel members raised a number of questions about sipuleucel-T and the trials that led to its FDA approval. Among them was whether the fact that many men in the sipuleucel-T arm of IMPACT eventually went on to receive docetaxel could have confounded the survival figures. But an additional analysis of the trial data presented at this year’s American Society of Clinical Oncology annual meeting showed that the treatment’s effect on overall survival appears to be independent of docetaxel use, Dr. Daniel Petrylak of the Herbert Irving Comprehensive Cancer Center at Columbia University told the committee.
In addition, approximately two-thirds of patients in the placebo arm “crossed over” (when they showed evidence of disease progression) to receive immunotherapy manufactured from cells obtained at trial entry but cryopreserved for possible later use, and several committee members expressed uncertainty about how that may have affected the survival results. However, according to Dr. Daniel George of the Duke University Comprehensive Cancer Center, an analysis to be presented at an upcoming meeting will show that there was a survival improvement in patients who received the frozen product.
“If anything,” Dr. George said, “that would decrease the [survival] benefit associated with Provenge.”
Based on an agreement with the FDA, Dendreon, which manufactures sipuleucel-T, is conducting a “registration trial” that will include at least 1,500 patients, to monitor efficacy and side effects associated with sipuleucel-T, said Dr. Mark Frohlich, the company’s chief medical officer.