Ipilimumab and vaccines

Seems like Fridays roll around all too quickly, but so far so good in making posts here. Most prostate cancer activists will know that at least two vaccines have shown promise for treating advanced disease, sipuleucel-T (Provenge™) and Prostvac. The former is approved and you can read everything you need to know about it on the Dendreon website. Recall that this is a commercial website, but it is required by the FDA to give a “fair and balanced” (to quote FOX) view of the treatment. What is not covered well there is the cost controversy. Scanning the web for what I thought was the best analysis of this issue, I found this blog, by a person who has a reasonable and dispassionate view I think. It starts off with an ad from an advocate, so be sure to scroll down below the ad to read Janet Fang’s commentary. We treat patients at our center with sipuleucel-T, and we have struggled with some of the cost issues. I have gone on record to say that I think Medicare should (and must) begin to look at cost controls, but they should do it across the board, not single out one drug for one disease. If we don’t get a handle on this, we can kiss our wonderful country goodbye as we in the health care field find increasingly expensive drugs with (unfortunately) limited, but real efficacy.

The second vaccine is Prostvac. We were also involved in the testing of this agent in this article by Phil Kantoff. Although this is not approved, there will soon be a large, randomized phase III trial to determine whether this agent really does produce a benefit. The reason for such a trial is well reviewed in this letter – often imperfections in smaller preliminary trials do not give the true picture of what is going on due to imbalance between patients who enter the trial.

So what about ipilimumab? Today, the FDA approved its use in cases of advanced or unresectable melanoma, a lethal form of skin cancer. The intriguing thing about the study that led to approval was that ipilimumab (an antibody that revs up the immune response) alone (response rate -RR- 10.9%) was actually superior to the use of vaccine alone (RR-1.5%) or in combination combination with the vaccine (RR-5.7%).  And the cost?? According to the WSJ, “Bristol plans to charge about $120,000 for a standard four-infusion regimen of Yervoy.” over three months, when the drug becomes available within weeks. This (like sipuleucel/Provenge) also is for a 4 month improvement in survival. If you want to run the numbers, Bristol acquired the drug by buying Medarex for $2.3B in 2009; so on a very oversimplified analysis, they would recover their cost by treating 20,000 patients (globally, there are 48,000 deaths per year from melanoma). If you want to know whether this is a good idea, please go back to paragraph one to read Janet Fang’s commentary.

But here, we are interested in prostate cancer. Ipilimumab could be used alone or in combination with one of the vaccines, and since the vaccines are more effective, seemingly, than the melanoma vaccine in the trials referenced we might expect better results (costs be hanged…). The UCSF team has already tried ipilimumab along with g-csf with some encouraging results.There are ongoing and planned trials of the combination of ipilimumab with prostate cancer vaccines. Let’s hope they work, and that someone much smarter than me can figure out how we can possibly afford all of this. Also, don’t forget that although the vaccines aren’t very toxic, ipilimumab caused serious side effects in ~13% of patients. This is because when you “mess with mother nature” by enhancing the immune system, you can unleash the immune cells to attack not only cancer cells, but the host.

We all know the names of such diseases: ulcerative colitis, lupus, thyroiditis, rheumatoid arthritis, and the rest… Does anyone remember yin and yang?