Lancet Editorial

[Christine MH-UK]

Herceptin and early breast cancer: a moment for caution

http://www.thelancet.com/webfiles/im.../herceptin.pdf
I found this editorial from the Lancet, a very well-respected British medical journal, interesting, although a bit discomforting. As a relatively young patient with a good heart, I think I'll take my chances with continuing to pay for it (my oncologist was on the HERA trial board and I think he knows more than is publicly available), but the editorial does raise a number of concerns.

Hey Christine,

Thanks for posting this--I hadn't seen it. And I can't get at the JAMA piece mentioned in it because that one you have to pay for.

I know how just about anything I read can make me uncomfortable about various treatment decisions we have made. But I think this editorial doesn't actually say a thing. It uses all kinds of weirdly indirect rhetorical formulations to cast doubt on the herceptin trials--even raising the specter of unethical drug company behavior in combining the data of two trials.

Now believe me I am first in line when it comes to distrusting the drug companies. And I know that loads of breast cancer activists are very suspicious of stopping trials early. And I am sympathetic to their concerns.

But these trials do not exist in a vacuum, as their editorial suggests. They build, first of all, from a well established precedent: every agent that has shown benefit in the treatment of metastatic breast cancer has gone on to have benefit in adjuvant treatment. In addition, these adjuvant trials build on data from a few smaller neoadjuvant trials with herceptin (at MD Anderson and Dana Farber) that showed remarkable activity for the drug.

It is true that we can't possibly have full overall survival data yet. We might never have true clear data here because of the crossover of so many women onto Herceptin from the non-Herceptin arm.

But this editorial does a real disservice. It is clear beyond a doubt, I think, that the women who will benefit from adjuvant herceptin far exceeds any number that will suffer permanent cardiac damage or death from the drug. I am sorry that Hortobagyi and others have thrown the other "c" word ("cure") around. Lord knows I hope it's true, but it certainly is premature to say that.

Thanks for posting--sorry if I sound grumpy. But I really hated that editorial

Jeff

[Christine MH-UK]

Hi Jeff,

I wasn't entirely happy with the editorial myself. In a way, it sort of undermines its own message by pointing out that three years ago NICE was criticised for delaying herceptin for secondary cancer. This point would really only be convincing if herceptin had later turned out not to be useful for secondary cancer.

It is not ideal that the researchers combined the results of two trials. I wonder if they did it to prove the thing that is really hard to prove with her-2 patients over such a short-time frame: that a new treatment can make a statistically significant differences in overall survival, not just recurrence. The irony with cancer treatments is that the better they get at keeping patients with secondaries alive, the harder they make it to prove that new treatments keep patients alive longer, yet that is what really matters. Perhaps the editors of the NEJM should have advised them to include some basic data from the two trials.

I suspect that the Lancet was having a go at the New England Journal of Medicine for allowing an editorial that went over the top. I agree that Dr. Hortobagyi's editorial may have done the drug an unintentional disservice. I know that a lot of people are very unhappy with herceptin being labelled a cure, as if it solved everybody's breast cancer problems by itself.

I am naturally skeptical about the drug companies myself, but in the NEJM it did make it seem like in the U.S. trials Genentech had only provided herceptin and a bit of funding. It does not seem to have been involved in the trial design.

[JohnL]

I understand that Roche were so appalled at this article they took an unusual step (drug companies keep their heads down when medicos are arguing as they'll only be accussed of being partisan) of fielding a spokesman.

The language was diplomatic, saying that Roche had "read the editorial and said that the statements it contained were not correct."

Which coming from an official Roche spokesperson is the equivalent of 'This man is an idiot and clearly does not know what he is talking about'. The implication being that the Lancet article was more political opinion about funding as a result of public pressure.

I understand a few other leading lights in the area have broadcast less oblique opinions about the article and its author.

JL

Thanks John and Christine for your additional input.

I do see that this seems to be a bit of a journal to journal spat. What is weird about it to me is how dishonest the Lancet piece is. The data they claim is missing from the NEJM piece is--unless I'm missing something--widely available all over the net. And was even partially presented at ASCO.

There is so much going on here that I don't understand--about the British health care system, US marketing of new drugs, etc.

But I think Christine is right: Overall Survival is the magic term in these trials. It's funny though because nobody at the Lancet kicked (as far as I can tell) about the publication of the ATAC trial data heralding the advance of Arimidex over Tamoxifen, even though the overall survival data is not clear here either.
The herceptin data from two trials was combined to give the results more statistical power--that is clear. But not, I think, out of any devious drug company machinations. Instead, I think, the pressure came from clinicians/investigators who were predicting--some more than a year ago (see Debu Tripathy's comments in breastcancerupdate, for instance) that there was absolutely no way that the results would be anything but strongly positive.

And hence, back to the ethical dilemma of what to do about randomization when the treatment arm is clearly getting benefit...

All the best,
Jeff

[Christine MH-UK]

Thank you for the quote, John. I used it to find a newspaper article on the matter, see below.

I feel rather offended that they describe an 'unholy alliance' between drugs companies and desperate breast cancer patients, which really smacks of backroom deals. I don't think that this is accurate at all and I would like some proof of collusion.

A lot of women have been working really hard to get their often very sad stories out there so they can get herceptin and have done so completely independent from the drugs companies. I got involved because really high-risk patients weren't getting herceptin ( such as a thirty-three year old with er-,pr-, inflammatory breast cancer, diagnosed while pregnant). The oncologists have been pressing for this as well.

Anyway, here's the URL for the story.
http://www.iht.com/articles/2005/11/09/news/lancet.php