Another day, another announcement of a potentially promising new cancer treatment, and another day of caution. Dendreon is the name of the company that issued the press release and has worked for years to develop the vaccine to treat advanced, hormone-refractory prostate cancer.
In today’s announcement, the company said that the vaccine—called Provenge--“met its primary endpoint of improving overall survival compared to a placebo control. The magnitude of the survival difference observed in the intent to treat population resulted in the study successfully achieving the pre-specified level of statistical significance defined in the study’s design. The safety profile of Provenge appeared to be consistent with prior trials.”
But not everyone is ready—just yet—to say the battle is won. And the advocacy community is poised and ready to fight back if anyone suggests we not accept today’s announcement as the final word as to whether or not this vaccine is effective.
Take for example the comments from the American Cancer Society’s chief medical officer, Dr. Otis Brawley, posted on-line today at Forbes.com:
“It certainly sounds good, but we really need to see the details…I will be watching with interest and some hope…Surprisingly, some companies often lack the expertise to fully analyze these trials appropriately,” (Brawley) says.
Within minutes after the story was posted, we started to receive emails criticizing our “wait and see” approach to the news. And we weren’t alone. Posts on the Forbes website claimed the author of the article was inappropriately downplaying the results of the study as well. The suggested “payback”? The author should get prostate cancer and be denied Provenge as a treatment.
The announcement from Dendreon is certainly hopeful news for the men in this country who have advanced prostate cancer. However, until the data is carefully reviewed we won’t know for certain how successful the drug really was in producing a meaningful response in what to date has been a very difficult cancer to treat when it spreads through the body.
This is a vaccine that has travelled a long and difficult road to get to today’s announcement. Provenge has sparked controversy in the past and has been the focus of ire from some in the prostate community who have railed against the FDA and others for not approving or supporting the vaccine despite the absence of clear evidence that the vaccine was effective.
Advanced prostate cancer is truly a disease in need of a treatment breakthrough. The American Cancer Society expected in 2008 that about 186,000 men would be diagnosed with prostate cancer, and 28,660 men would die from the disease (data for 2009 projections is still not available). The good news is that the frequency of new cases and deaths from prostate cancer have been declining in this country.
But for men who either diagnosed after the disease has spread, or who recur after primary treatment with surgery or radiation therapy, the outlook is grim. Hormonal manipulation usually works for a period of time, but is not without side effects that negatively impact the quality of life. And for men who have more aggressive disease that escapes from the hormone treatments, there is little to offer in terms of truly effective chemotherapy. Advanced prostate cancer can linger for a long time, and frequently causes severe symptoms with pain being a frequent and severe problem.
So any new treatment that might improve survival and quality of life for men with advanced prostate cancer would be truly welcomed.
There is another wrinkle to this story that is equally important, and that is the fact that if this vaccine is successful, it will be the first time a vaccine has shown any lasting, confirmed benefit in the treatment of cancer. Truly, in a sense, this could be the answer to a search that has dogged and defeated cancer researchers literally for decades as they have tried to manipulate our bodies’ own immune systems to help defeat cancer.
We won’t have any real information to look at until the data from the clinical trial is presented at a national urology conference on April 28. Certainly many eyes and ears will be focused on that presentation, not the least of which will be members of the investment community. Even then, the presentation will offer only a snapshot into the effectiveness of Provenge.
As I write this, we don’t know exactly what the data will show. The company is prohibited from releasing that information to anyone prior to the presentation. But we do have a glimpse as to what we might expect, based on a conference call the company held with investment analysts earlier today.
Here is a snapshot of the call:
First, the company would go no further with the details of the data except for what they put in the press release. They did mention that their report today was “top line” and that further analysis of the trial information was necessary.
The CEO of the company, Dr. Mitchell Gold, went on to say that the results of the trial were “unambiguous”, and that the trial clearly hit is target endpoint. When pressed to define that endpoint, Dr. Gold declined to provide more information, citing the need to hold back any further comments pending the presentation in two weeks.
Dr. Gold also mentioned that the median survival in the trial was consistent with other studies of Provenge, and that the vaccine clearly prolonged the overall survival of the patients who either received the vaccine or were supposed to receive the vaccine (called an “intention to treat” analysis, which is appropriate). He also mentioned that some patients who were in the placebo group did cross-over at a later date to receive another formulation of the vaccine. These patients remained in the placebo group as part of the analysis reported today, which means it was even more difficult for a difference to be noted in favor of the vaccine in the treated group if the vaccine had any positive benefit.
Dr. Gold emphasized repeatedly during the call that the analysis was only “top line” and that the company has not had a lot of time to examine the data. Nonetheless, in response to several questions, he indicated that the company is planning on resubmitting an approval application to the FDA in the latter part of 2009, and is already examining ways to initiate marketing and manufacturing for Provenge.
There were several comments during the call stating that the results of the current trial support improved survival for men with advanced prostate cancer who received the vaccine as seen in prior Provenge phase III clinical trials of the vaccine.
The company is clearly enthusiastic about the results. Those of us without access to the information still don’t have as clear a picture as we would like, and we look forward to the actual presentation in late April.
In a phase III trial reported in the Journal of Clinical Oncology in July 2006, researchers reported a 4.5 month increase in median survival (25.9 months for men treated with the vaccine, compared to 21.4 months for men who received a placebo instead). However, in that same study, the vaccine did not improve the time-to-progression for men who received the vaccine (11.7 weeks for vaccine vs. 10 weeks for placebo).
For whatever reason, in that particular trial, it appeared that the vaccine had little effect on one important measure (time to progression)—which actually occurred fairly quickly in a matter of about 3 months—compared to the survival advantage, which took almost 2 years to become evident.
I don’t know if the current trial measured quality of life for the men who received the vaccine, but given the fact that advanced prostate cancer frequently attacks the bone and can cause significant pain, I hope that the vaccine—if in fact it is shown to be truly effective—can do something to control the symptoms of advanced prostate cancer. Simply stated, if the disease progresses quickly with or without the vaccine, living an extra 4 months in agony may be worthwhile to some men, but may not be worthwhile to others.
So, the bottom line is that we anxiously await the presentation of the data and a more detailed review which will hopefully follow in the near future.
We hope the response to the vaccine is a meaningful one, in terms of days of life and the quality of life. And we hope that this vaccine will in fact demonstrate once and for all that we are in fact able to effectively use a vaccine to “wake up” our bodies own natural defense mechanisms to treat a notoriously difficult disease.
If this vaccine does meet those goals, this will be a major step forward on several fronts. Unfortunately, we have learned time and again that however glowing the press reports, until “the data is in”, we won’t know for sure.