Hyped Melanoma Drug Trial Proves Only That Big Pharma Will Do Anything to Sell Its Poisons

by Heidi Stevenson

6 June 2010

In yet another display of Big Pharma's mastery at creating hype for its drugs, a new trial is thrilling oncologists and Big Media. Fully funded by the companies hoping to profit, Bristol-Myers Squibb and its new acquisition, Medarex, the study purports to show that ipilimumab effectively treats the aggressive skin cancer, melanoma.

Bristol-Myers has been trying to find a cancer that its drug, ipilimumab—which will cheekily be called ippy from here—can treat. They appear to have given up on the idea of cure. However, their presentation at the 46^th Annual Meeting of the American Society of Clinical Oncology convinced many of the doctors attending that it's the best thing since...well, since selling the public on the idea that they have something to offer in cancer treatment.

As has been documented here, ippy has been tried as a cancer treatment many times without success. Attempts to affect early stage cancers have met with dismal results, so the latest approach has been to go for the gold (literally) and see if they can cobble together some sort of study that seems to indicate some sort of benefit in advanced cancer patients. The result is now being obediently hyped in mainstream media.

The Ippy Trial

The trial was reported in the New England Journal of Medicine. It was a Phase 3 study of melanoma patients whose cancer could not be treated surgically. They had previously been treated with other methods, but their cancers had metastatsized.

The drug trial did not compare ippy with a placebo, though they did try to give that impression by using placebos in addition to drugs, but never alone. Instead, they chose to compare ippy with an unproven and unapproved drug called gp100.

Potential subjects were eliminated if they suffered from diarrhea or any other condition the trial designers decided were indicative of any immune system disorders. [One must wonder how anyone with a diagnosis of cancer could have qualified! —Ed.]

Melanoma sufferers whose cancer had metastasized to the central nervous system were eliminated. Since 40-60% of all melanoma patients have brain metastases, this means that about half the potential advanced melanoma patients were not considered candidates for ippy. So, whatever the benefits shown by the trial, we can halve them to better correlate with reality.

A total of 676 melanoma patients were enrolled. Drugs were given to patients in a ratio of approximately 3:1:1. That is, about three times as many were given ipilimumab plus gp100 as either ippy alone or gp100 alone:

Number of Enrolled Subjects
Ippy Plus Gp100	Ippy Alone	Gp100 Alone
403	137	136

By the end of 55 months, all the patients had died. Neither ippy nor gp100 saved any lives. At the end of two years, the results didn't look much better. At 12 months, 63% of all the patients had died. At the end of two years, 86% of the patients were dead.

Nearly all the patients had adverse events during the study: 98.4% of the ippy + gp100, 96.9% of the ippy alone, and 97% of the gp100 alone. No discussion of how these events affected quality of life was included in the study, though they included vomiting, abdominal pain, decreased appetite, fatigue, headache, cough, difficulty breathing, anemia, pruritis, rash, vitiligo, diarrhea, colitis, and other disorders that obviously diminish comfort and pleasure in life.

Here are the number of patients from each group who were still alive at 4, 8, 12, and 24 months:

Number (Percent) of Patients Alive
Number of Months	Ippy Plus Gp100	Ippy Alone	Gp100 Alone
4	297 (73.70%)	106 (77.37%)	93 (68.38%)
8	223 (55.33%)	79 (57.66%)	58 (42.65%)
12	163 (40.45%)	56 (41.18%)	32 (23.35%)
24	54 (13.40%)	24 (17.65%)	16 (11.68%)

A serious anomaly shows up in this table. Notice that the combination of ippy and gp100 seems to indicate a poorer result than ippy alone? One must wonder if, perhaps, gp100 causes more deaths than placebo. These results might indicate that to be the case. If so, then this entire trial is nothing but a hoax.

The authors claim that the median length of survival was 10.1 months in patients who received ippy alone, 10.0 months in those who received ippy + gp100, and 6.4 months in patients receiving gp100 alone. That sounds impressive—if you don't look at the study as a whole.

There are several glaring flaws in this trial, and the most obvious is the lack of a placebo. It's quite interesting that modern medical pseudoscience insists that a placebo be included in any non-pharmaceutical trial, but seems to have no problem when one isn't used in a trial of a Big Pharma product. In this case, the situation is even worse, since ippy is being compared with an unapproved drug, one that has no track record.

On looking at the actual results in terms of percentages of patients alive over the first two years, the results become downright suspicious. By combining the drug being tested with the control (gp100), a serious anomally becomes apparent:

When ippy is combined with gp100, the number of dead patients increases over ippy alone.

That would indicate that the trial compared ippy against a drug that decreases lifespan.

And that would explain why ippy wasn't trialed against a placebo.

A placebo would do better than a drug that kills more patients than it helps—and it looks like gp100 may do just that, at least in this sort of patient. So, the only benefit this trial seems to show is that ippy helps counteract the ill effects of another drug.

It's [slightly] possible that the action of ippy is depressed when in combination with gp100. But it flies in the face of logic to believe the researchers chose to compare ippy with gp100—instead of the so-called "gold standard" of a placebo—without having some idea of what the results would be.

The Hype

Oncologist Stephen Hodi, a lead researcher on the trial, stated, "This is paradigm-shifting. It is hopefully the beginning of a new golden age of melanoma treatments." Perhaps...as a new method of giving the impression of efficacy and hyping a drug.

Robert Langreth, a senior editor at Forbes, is hyping ipilimumab. (One must wonder if he has stock in Bristol-Myers.) He goes so far as to tell a tale of a patient on the trial, claiming that she "was on death's door a few years ago. Melanoma had spread all over her body and conventional treatments had failed. Then, in 2005, she [took] the Bristol drug, ipilimumab. It worked—even as the drug failed to help numerous other patients. The 29-year-old remains cancer free today."

That's a nice story—but he doesn't explain how she survived, when the study itself reports that all the subjects died!

This, though, is how astroturf is created. How many patients with melanoma will read about this trial and start clamoring for ippy?

How many patients will suffer from falsely raised hope? How many millions or billions of dollars will be tossed down this pharmaceutical rabbit hole? Is there truly no limit to how low Big Pharma will go in order to make a killing?

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