Long-awaited vaccine offers a ray of hope for some men with advanced prostate cancer
The U.S. Food and Drug Administration's (FDA's) approval of sipuleucel-T (Provenge)the first vaccine for the treatment of cancermarks an important milestone in the war against prostate cancer. Provenge doesn't prevent prostate cancer (in the sense that most traditional vaccines prevent disease) or cure it, or even slow its spread. But it does prolong life in some men with advanced prostate cancer.
The extra time, slightly more than four months, is modest, at best, but important because it is proof that a cancer vaccine to boost the immune system can prolong life, suggesting that future vaccines might be even better.
Rocky Road to Approval
Unlike traditional vaccines, this type of vaccine, also called cancer immunotherapy, is designed to help a person's immune system recognize its own cancerous cells as foreign. Once the cancer cells are perceived as intruders, the person's immune system can mount an attack against them.
However, this is particularly challenging with prostate cancer because a man typically has had the disease for several years before it metastasizes. During that period, his immune system has seen the cancer but has grown complacent.
In spite of the challenges inherent in this approach (researchers have been studying Provenge for 15 years), data show that Provenge does prolong life. And in May 2007, an FDA advisory board recommended its approval.
The decision was based on results from two clinical trials that showed that while Provenge did not prolong the time until the disease had spreadthe yardstick by which success was to have been measuredit did improve survival.
Although the FDA typically accepts its advisory board's recommendations, in the case of Provenge it did not. The finding that the vaccine failed to meet the intended endpointa delay in disease progressionraised concerns that the modest improvement in survival simply occurred by chance.
Although proponents of the vaccine argued that survival time, not time to disease progression, was the yardstick by which the vaccine's effectiveness should have been measured, the FDA put the approval on hold pending further data from a study known as the IMmunotherapy for Prostate AdenoCarcinoma Treatment trial, or IMPACT. This time, however, the FDA agreed to accept survival rather than disease progression as the measure of success.
The Impact of IMPACT
The IMPACT trial examined 512 men, 341 of whom received an infusion of Provenge every two weeks for four to six weeks and 171 of whom received a placebo. The results of this trial, which were reported last year in The New England Journal of Medicine, also showed that like the earlier trials, time to disease progression did not differ significantly between the two groups.
However, the vaccine did improve median survival: about 26 months for those receiving Provenge versus 22 months for the men who received the placebo. The median three-year survival was also higher for the Provenge group than the placebo group, 32 and 23 percent, respectively.
While an extra 4.1 months of survival may not sound impressive, it's nearly twice as long as the median survival for men using the chemotherapy drug docetaxel (Taxotere). The only other approved treatment for such patients, Taxotere improves overall survival by 2.4 months on average. The data showing improved survival, coupled with a tolerable side effect profilethe most common side effects were chills, fatigue, fever, back pain, nausea, joint pain, and headacheled the FDA to grant approval.
Provenge is approved only for men with advanced cancer who have not responded to other treatments like hormonal therapy and are experiencing few or no symptoms. But even if you're a candidate, getting the treatment might still present a challenge. Two issuesavailability and affordabilitythreaten to limit access to it.
Availability. According to Dendreon Corporation, the company that developed Provenge, the vaccine will initially be manufactured in a limited number of facilities. Consequently, in the first year of production, treatment will be available for only 2,000 patients and only through the 50 clinics that participated in the clinical trial. Fortunately, however, that appears to be a short-term issue. When Dendreon expands its manufacturing, as it intends to do in the middle of 2011, the drug is expected to become more widely available.
Affordability. The cost of Provenge$93,000 for three infusionsand how Medicare and private insurance companies decide to handle the costs may be long-term issues. The federal Centers for Medicare and Medicaid Services (CMS) has started the process of deciding whether paying for Provenge is reasonable and necessary.
CMS expects to make a final ruling by July 2011 at which time it will issue a National Coverage Determination (NCD). Until the NCD is issued, however, regional Medicare carriers are free to decide whether to cover the cost of the vaccine. In addition, at least one private insurer, Aetna, has agreed to provide coverage.
Dendreon has also set up a patient assistance program. For additional information about the vaccine, visit the website at www.provenge.com or call 877-336-3736.
While the FDA's approval of Provenge is a victory, it is not the end of the fight. Researchers are already studying a number of ways to improve the vaccine's effectiveness. For example, investigators at Johns Hopkins have found that combining Provenge with androgen deprivation therapy increases the chances of stopping the cancer early on. Similarly, investigators have found that combining Provenge with radiation therapy also appears to have a synergistic effect.
Provenge is also being tested in several other clinical trials, including a phase 3 study called Provenge Treatment and Early Cancer Treatment (PROTECT). This study involves men with early-stage, non-metastatic prostate cancer. Many experts believe that immunotherapy may be most effective in men who have earlier-stage disease.
Newer vaccines also are under development. In one phase 2 study, a vaccine called Prostvac prolonged median survival by 8.5 months. However, like Provenge, Prostvac failed to improve time to disease progression. If Prostvac makes it through the FDA approval process, it promises to be cheaper than Provenge, since it does not have to be customized for each patient and will be available "off the shelf."