Trastuzumab emtansine aka trastuzumab-DM1 aka trastuzumab-MCC-DM1, abbreviated to T-DM1 is an antibody-drug conjugate consisting of the antibody trastuzumab (Herceptin) linked to the cytotoxin mertansine (DM1).
Right now it’s still in Phase III randomized clinical trials for breast cancer treatment. It’s makers, Genentech, are part of Roche.
Roche clearly wants to pump up it’s stock (after the disaster of rejection in 2010) and that means preemptively creating a demand for T-DM1 by priming the media pump.
Sow what better than getting MSNBC to make the public aware of this “miracle drug”.
The reports starts;
ROBERT BAZELL reporting: It is a new kind of drug, the so-called magic bullet that attacks a type of breast cancer while preserving quality of life.
I might be in the minority here, but whenever I hear the phrase “magic bullet”, I take it to be a negative story on science, due to it’s association with the JFK assassination and the perversion of science. But I’m willing to accept this is a genuine case of hyperbole.
But wait… haven’t’ we heard of T-DM1 before?
Now many years back I worked for a UK based clinical research company and I understand the mechanisms of the double-blind methodology. But does this sound like it to you?
BAZELL: Fern Saitowitz was one of almost 1,000 women in the study out today. All had advanced breast cancer of a type called HER2 -positive that is especially aggressive. The standard treatment is a custom-made antibody called Herceptin that attaches to the cancer cell , but must be combined with regular chemotherapy. The new drug called T-DM1 links the Herceptin antibody with a powerful toxin. The antibody travels through the bloodstream and attaches to the cancer cells , delivering the poison directly, sparing the healthy cells and eliminating the need for additional chemotherapy.
After two years, 65.4 percent of the women on T-DM1 were alive compared to 47.5 percent of those on the standard treatment . The doctors at the convention here in Chicago are impressed enough with those results that they expect they’re likely to get much better when the drug is given to women with much less advanced breast cancer . And because the toxin only goes into the cancer, the side effects are relatively mild compared to the standard chemotherapy.
Now I’m all for targeted treatment for anything, who wouldn’t be. Clearly trying to kill something in the body by poisoning that majority of it is clearly stupid. But the figures posted are suspicious in that they are not valid clinical trial results, not in the true random double blind sense.
For one, T-DM1 was prescribed to a distinct set of patients, fitting a certain profile. Not to mention that fact that the actual benefits of combined therapy were not well proven when compared to other therapies.
And how small was that Phase II study?
The FDA submission was based on a Phase II study known as TDM4374g, a single-arm, multi-center trial designed to assess single-agent T-DM1 in 110 women with advanced HER2-positive breast cancer whose disease had worsened after receiving at least two prior HER2-targeted treatments (Herceptin® [trastuzumab] and lapatinib) in the metastatic setting, as well as an anthracycline, a taxane and capecitabine.
Little wonder then that their condition improved by nearly 18% when the alternative “standard treatment” made them worse.
It’s the reason why the FDA REJECTED approval in 2010.
Or as they put it.
In its review of the BLA, the FDA stated the T-DM1 trials did not meet the standard for accelerated approval because all available treatment choices approved for metastatic breast cancer, regardless of HER2 status, had not been exhausted in the study population.
Now that must have really annoyed Roche,mainly because Genentech took a major mauling on the stock exchange. So they begrudgingly went ahead with their Phase III study as per this note;
Genentech will submit data from the amended Phase III randomized EMILIA study to the FDA to support a new T-DM1 BLA in mid-2012. The EMILIA study compares T-DM1 to lapatinib in combination with capecitabine in people with advanced HER2-positive breast cancer whose disease has worsened after receiving initial treatment.
That’s basically now and they really need to not only put pressure on the FDA to grant approval, they need to get the public pushing Doctors to prescribe it. Remember also that once they get the FDA to approve it, they’ll switch attention to the UK in order to get NICE to approve it so they can get the NHS buying it. Which is why the Daily Mail is on board with a story like this “Breakthrough breast cancer drug can extend life of sufferers who have one of disease’s most deadly forms”, published just a few days ago.
Now it could be that Roche is setting great stall on it’s small Phase II study’s 17.9% “improvement” figure; and perhaps this has been repeated in the wider and random Phase III study. But if it has, this would be exception to the rule over similar studies. By setting such a finite criteria, I’m actually more surprised the results were not better.
My only real point is the way big Pharma manipulate the public with “public relations2 releases to create a demand for an unproven unapproved treatment.
One thing to note most about T-DM1 is that is doesn’t state it cures the cancer , just that it “extends life”.
In any case, it will be hugely expensive.