Study: Prostate cancer vaccine extends survival

CHICAGO, 10 may 2009-- — An experimental treatment added four months to the lives of men with advanced prostate cancer in a study that tested an entirely new approach to fighting the disease, doctors reported today.

Dendreon Corp.’s Provenge vaccine trains the immune system to fight tumors. It’s called a “vaccine” even though it treats disease rather than prevents it.

Doctors have been trying to develop such a therapy for decades, and this is the first to meet a preset goal for improving survival in late-stage testing.

“There have been a lot of false starts, but this is a real start,” said Dr. Paul Schellhammer, a urologist at Eastern Virginia Medical School in Norfolk, Va., who led the study. Results were reported today at an American Urological Association conference in Chicago.

Seattle-based Dendreon paid for the study, and Schellhammer owns stock in the company. Dendreon shares fell sharply, and then trading was halted leading up to the release of the data. Shares fell $9.74, or 45.2%, to $11.81. The reason was not immediately clear.

Four months may not sound like a lot, but it is longer than the three months afforded by Taxotere, the only chemotherapy approved for men in this situation.

Doctors hope for even greater benefit if they give the drug earlier in the course of the disease. Dendreon would give no cost estimate for Provenge, but other such biotech drugs cost several thousand dollars a month.

It remains to be seen if side effects will keep Provenge from winning federal Food and Drug Administration approval. Two years ago, the FDA went against its advisers and delayed a decision, asking for more proof of safety and effectiveness.

The new study involved 521 men whose cancer had spread and wasn’t responding to standard hormone treatments. Two-thirds were given Provenge, a treatment that is customized for each patient.

Doctors collect special blood cells from each patient that help the immune system recognize cancer as a threat. They are mixed with a protein found on most prostate cancer cells and another substance to rev up the immune system. The resulting “vaccine” is given back to the patient as three infusions two weeks apart.
The other one-third of men in the study had a dummy infusion.

Median survival was 26 months in men given Provenge and 22 months in the others. Three-year survival rates were 32% for the Provenge group and 23% for the others — a 38% improvement.

Strokes and other brain-related problems were no more common with Provenge — a worry raised by earlier studies. However, four men given Provenge suffered lung clots, though none were fatal. High blood pressure was twice as common with Provenge. Overall, the rate of serious side effects was the same in each group.

Improving survival “is the gold standard” for any treatment, and Provenge appears to do that, said Dr. Ira Sharlip, a urologist from the University of California in San Francisco and a spokesman for the urological association.

Dr. Otis Brawley, the American Cancer Society’s chief medical officer, said the FDA had been right to ask for more study. Seeing the new results, he said, “I would vote for approval” as long as it didn’t harm men’s quality of life.

One patient said it did not hurt his. Thomas Robbins, 74, of Forest City, N.C., was diagnosed in 2002 with prostate cancer that was growing despite hormone treatment.

“They wanted to give me chemo,” but he feared its side effects and enrolled in the Provenge study instead. He learned afterward that he had been one of those given the vaccine.

“Did it help me? I can’t 100% guarantee, but I think it did,” he said.

Advocacy groups cheered the results. Scott Riccio, founder of Accelerate Progress, called them “compelling.”

“For the first time, we have real clinical validation that cancer can be fought by stimulating the body’s immune system,” he said in a statement. “Hundreds of thousands of men fighting prostate cancer will now have real hope that a safe and effective new option will be available to them in their fight for life.”

Thomas Farrington, a prostate cancer survivor and founder of the Prostate Health Education Network, said: “Prostate cancer patients finally have hope for a better life. We are in desperate need of groundbreaking new treatments like Provenge.”

Prostate cancer is the most common non-skin cancer in American men. An estimated 186,000 new cases and 28,660 deaths from it occurred last year.

Company says prostate cancer vaccine shows promise

By MARILYNN MARCHIONE

16 april 2009--An experimental treatment that takes an entirely new approach to fighting prostate cancer extended survival in a late-stage study, its maker announced Tuesday.

Seattle-based Dendreon Corp. said that its Provenge cancer vaccine improved overall survival when compared to a dummy treatment in a study of 512 men with advanced disease.

No survival details or information on side effects were given. Full results will be presented at an American Urological Association meeting later this month, and Dendreon said it would seek federal approval of the treatment later this year.

Provenge is not like traditional vaccines that prevent disease. It's a so-called therapeutic vaccine that treats cancer by training the immune system to fight tumors. If approved, Provenge would be the first such treatment on the market.

This is the second major study in which Provenge has shown a survival benefit, leading some scientists to hope not just for its approval but for a new approach to fighting cancer beyond the surgery, radiation, hormones and chemotherapy used now.

"This is an exciting result, demonstrating that harnessing a patient's own immune system can successfully attack prostate cancer," said Dr. Eric Small, cancer specialist at the University of California at San Francisco. "Now we have more confidence that the initial results we saw were real."

He enrolled some patients in the new study and led the earlier one, but has no financial ties to the company or the vaccine.

In the earlier study of 127 men, those treated with the vaccine lived an average of 4 1/2 months longer than those given dummy treatments. After three years, survival was 34 percent in the vaccine group and only 11 percent in the other.

Those results led advisers to the Food and Drug Administration to recommend Provenge's approval two years ago. But the FDA delayed action and asked for more data, because extending survival wasn't the main goal of that study — slowing progression of the cancer was, and the vaccine failed to do that.

The decision sparked protests from men's groups and cancer advocates because the vaccine did prolong survival, which they considered a more important result.

On Tuesday, results of the new study boosted Dendreon stock by $9.69, closing at $16.99, more than doubling in value as investors bet on improved chances of FDA approval and the potential for a lucrative market.

Provenge is a treatment that is customized for each patient. Doctors collect specialized cells from each patient's blood. Those cells help the immune system recognize cancer as a threat, much as it would germs that enter the body.

The cells are mixed with a protein found on most prostate cancer cells to help activate the immune system. The resulting "vaccine" is given back to the patient as three infusions two weeks apart.

So far, the vaccine has been tested on men with cancer that has spread beyond the prostate and is no longer responding to hormone treatments to curb its growth.

If Provenge proves safe and wins approval, "it would be an important breakthrough," said Dr. William Oh, a cancer specialist at Dana-Farber Cancer Center in Boston. Three years ago, he consulted for Dendreon on the vaccine but has had no financial ties to it since then.

"There are so few treatments available" for men whose prostate cancer has spread widely — a situation that affects 40,000 to 60,000 American men, he said.

Prostate cancer is the most common non-skin cancer in American men. An estimated 186,000 new cases and 28,660 deaths from it occurred last year.

Prostate Cancer Vaccine Before Hormones May Boost Survival

By Crystal Phend
BETHESDA, Md., 11 july 2008-- For nonmetastatic castration-resistant prostate cancer, an investigational poxvirus-based PSA vaccine given before second-line hormone therapy, rather than the reverse approach, might confer a survival advantage, researchers here found.
In a small randomized trial, median overall survival for men given the vaccine at any point tended to be extended by almost two years compared with those given the antiandrogen drug nilutamide (Nilandron) alone (median 5.1 vs. 3.4 years, P=0.13), reported Jeffrey Schlom, Ph.D., of the National Cancer Institute here, and colleagues in the July 15 issue of Clinical Cancer Research.
But patients who got the vaccine first had significantly improved survival (median 6.2 versus 3.7 years, P=0.045).
No treatment has been shown to prolong survival or time to metastatic disease in this group of patients, and there is no standard of care for them, the researchers said.
An earlier report from the trial showed longer time to treatment failure with the vaccine alone compared with nilutamide alone (9.9 versus 7.6 months) as well as for those given the vaccine after nilutamide failure (total 25.9 months).
The phase II study included 42 men with rising PSA despite castrate levels of testosterone below 50 ng/dL and no radiographic evidence of metastasis.
Patients were randomized to initially receive nilutamide (300 mg/day then 150 mg/day after the first month) or the recombinant poxvirus-based PSA vaccine with monthly booster shots.
Patients who continued to have rising PSA levels after six months but still no evidence of metastasis were offered combination therapy, which 12 patients in the vaccine group and eight in the nilutamide group accepted.
The retrospective analysis of overall survival at a median 4.4 years of follow-up found a trend to longer overall survival in patients given the vaccine alone versus nilutamide alone (median 5.1 versus 3.4 years, P=0.13).
Vaccine-treated patients also had a higher probability of survival at three years compared with those who received nilutamide alone (81% versus 62%).
For patients who went on to receive combination therapy at PSA progression, survival probability at three years was greater when the vaccine was started before rather than after nilutamide (100% versus 75%).
Overall survival was significantly extended when the vaccine was given before nilutamide initiation (median 6.2 versus 3.7 years, P=0.045).
Overall survival from the time of treatment crossover showed the same significant benefit of vaccination before nilutamide initiation (4.8 versus 2.8 years, P=0.028).
Prostate cancer patients more likely to benefit from vaccine therapy were those with:
A Gleason score of 7 or less (median OS 5.9 versus 3.1 years, P=0.033).
A confirmed history of radiation therapy (median OS 5.9 versus 3.1 years, P=0.018).
An on-study PSA of less than 20 ng/dl (median OS 5.1 versus 2.6 years, P=0.013).
Both lower PSA and Gleason score are consistent with less pathologically aggressive disease and lower tumor volume, and prior radiation may act as an immune booster by increasing cross-presentation of tumor antigens to T cells, the researchers said.
This suggested, "vaccine-based therapy should be utilized in patients with a lower tumor burden that allows the immune system to mount an effective response," they wrote.
None of the participants had previously received chemotherapy, but Dr. Schlom and colleagues noted that a previous study of metastatic cancer showed less effective T-cell response to vaccine with more chemotherapy treatments.
The researchers cautioned, though, that the crossover findings were based on small, retrospectively determined cohorts. Including only a subset of patients retrospectively determined to have received crossover treatment may have biased the findings by selection for healthier patients and elimination of those with rapidly progressing disease.
"However, even accounting for these limitations it is clear that patients with tumor characteristics consistent with slow growth and small volume, and who received vaccine earlier in their treatment regimen, may exhibit improved overall survival," the researchers said.
The study was funded by the National Cancer Institute. The researchers provided no information on conflicts of interest.
Primary source: Clinical Cancer ResearchSource reference:Madan R, et al "Analysis of overall survival in patients with nonmetastatic castration-resistant prostate cancer treated with vaccine, nilutamide, and combination therapy: implications for vaccine clinical trial design" Clin Cancer Res 2008.

FDA advisers OK prostate cancer vaccine

34 minutes ago
Federal health advisers have endorsed an experimental vaccine to treat advanced prostate cancer as safe and effective.
The Food and Drug Administration advisers voted unanimously Thursday to say Provenge is safe. They then voted 13-4 to say there is substantial evidence that it works in treating advanced prostate cancer that no longer responds to hormone treatment.
The FDA isn't required to follow the advice of its advisory committees, but it usually does. A final FDA decision on whether to approve Provenge, also called sipuleucel-T, is expected May 15. The vaccine is made by Seattle-based Dendreon Corp.
If approved, Provenge would become the third cancer vaccine but the first that is therapeutic. FDA-approved vaccines against liver and cervical cancer are both preventive.
Neither of two studies Dendreon submitted to the FDA in support of its application achieved their primary goal in showing Provenge delayed the progress of the disease, according to the agency.
However, the results of the first study suggested the vaccine could extend the lives of patients by 4.5 months compared to those given only dummy treatment. The only other prostate cancer drug shown to prolong the lives of patients is Taxotere, also called docetaxel.
A larger, ongoing study of Provenge is looking specifically at whether it increases longevity of prostate cancer patients.