BBC--herceptin shown to save lives (listen up NHS!!)

[Lani]

(NHS is ENGLAND's National Health Service)

Herceptin 'shown to save lives'

Herceptin is an expensive drug
Research provides strong evidence that controversial drug Herceptin is effective at treating the early stages of a certain type of breast cancer.
The drug was only approved by the NHS to treat early stage breast cancer last year after a long-running campaign.

The Lancet study, by London's Royal Marsden Hospital, provides the science to underpin that decision.

It showed the drug reduced death rates among women with early HER2-positive breast cancer.



Up to 25% of all breast cancers are of this hormone-sensitive type.

The Marsden team gave Herceptin to 1,703 breast cancer patients for one year after surgery and chemotherapy. Another 1,698 women did not receive the drug.

Ninety women in the control group died, but there were only 59 deaths among those given Herceptin (technical name trastuzumab).

Overall, Herceptin reduced the absolute risk of death by 1.8% over two years - effectively saving one extra life for every 55 patients treated.

Side effects

However, there were more serious side effects - including a raised risk of heart failure - in the Herceptin group.

Lead researcher Dr Ian Smith, from the Royal Marsden Hospital, London, said: "Our results indicate that trastuzumab shows a significant overall survival benefit in early breast cancer over observation alone after chemotherapy.

"The survival benefit that has emerged over such a short period emphasises the potential of this approach and underlines the importance of developing further specific targeted therapies in breast and other cancers."


Any drug getting approval for such widespread usage has to be properly evaluated by Nice, and would never just be rushed into use as a result of publicity
Department of Health

Herceptin was approved for use in treating early stage breast cancer by the National Institute for health and Clinical Excellence (NICE) last August.

This followed legal action - and a high profile media campaign - by protestors, who argued it was wrong to deny patients a drug which could potentially save their life.

However, a study published in the British Medical Journal in November questioned the merits of the NICE ruling.

The researchers, at the Norfolk and Norwich University Hospital NHS Trust and the University of East Anglia, warned that paying for Herceptin would mean treatment for other cancer patients would have to be dropped to "balance the books".

They called for NICE to say what should be cut to fund new drugs. The drug costs around £20,000 per year.

Professor John Toy, Cancer Research UK's medical director, said the findings showed the benefits of Herceptin gradually diminished after stopping treatment.

"Although Herceptin is clearly a valuable new treatment, questions remain about how long it's best to prescribe it for and how best to combine it with other breast cancer treatments."

Maria Leadbeater, of the charity Breast Cancer Care, agreed: "Clearly there remains the need for further research into the long-term effects of Herceptin, which will enable us to establish the ideal duration of treatment along with a more thorough understanding of its side effects."

A spokeswoman for the Department of Health said: "The NICE process for approving Herceptin for use in the NHS was fast-tracked through by the Department of Health, and was certainly not only given approval as a result of court cases.

"Any drug getting approval for such widespread usage has to be properly evaluated by NICE, and would never just be rushed into use as a result of publicity."

[Christine MH-UK]

There are alot of really bad politics surrounding herceptin in the UK. Non-breast cancer oncologists are basically afraid that it is going to eat up the cancer budget, so they are playing up all the potential problems. For example, they highlight that the possible long-term effects are unknown, even though this is true of just about every recent medicine, including ones that are for much more minor conditions. If it were cheaper, it wouldn't have half the problems. Unfortunately, some of this skepticism has even trickled down to cancer patients (there is at least one who was seriously considering not doing herceptin, even though she was high risk, that's how crazy it has gotten).

I really hope that that M.D. Anderson combo you posted about gets tried out in a bigger trial, since that seems to be both extremely effective and cost effective. Not to mention that it was done with just 24 weeks of treatment. So, less time in treatment for patients, less work for the oncologists and the oncology nurses and less expense for the health service. An all-around winner if it works out it a larger trial.

[Christine MH-UK]

Hi Lani,

I looked at the Lancet article and the accompanying editorial and I think that the news article presented an overly optimistic view of what the Lancet actually said about the two year follow up of the HERA trial.

Part of the reason I looked at it was that this "news" hardly seemed new and there was no mention of disease-free survival. The bad news is that the reduction in risk of recurrence or death from any cause has dropped from 46% at one year followup of this trial to 36% at the two year followup. Because this particular use seems to be less effective that formerly believed, it is also less cost effective and the health economists who judged it to be cost effective (at £18,500 per quality adjusted life year) for NICE note that it is now out of the range where it is unquestionably cost effective (i.e. each QUALY is now over £20,000). If the cost per QALY rises above £30,000, then THIS use of herceptin might be stopped, so more cost effective uses of herceptin are essential to ensure this drug's availability.

There are, of course, trials with better reductions in recurrence with longer followup, but the problem is that all of the big US ones cannot be considered because adriamycin, the anthracycline used in the trials, is not common in the UK. A recent Canadian study demonstrated that the current standard UK treatment of FEC was much more effective than AC->taxol, so this seems to have been a solid decision on the part of NICE.

FinHer is comparable to UK treatments and ticks some of the boxes (lowest cardiotoxicity, best risk reduction of any herceptin trial, much lower cost), but at three years followup had not demonstrated a statistically significant improvement over the control group, although probably because it was underpowered with just 231 women in the whole trial (versus over 2,000 for the next smallest trial).

Rather chillingly, the editorial mentions that New Zealand has turned down herceptin for funding, although it might consider adopting the FinHer regime. Now, I would love to see the shorter regimes fully tested out in a trial and, if New Zealand were thinking about running a trial I would praise them greatly, but that's not what they are thinking of doing. I have heard that some of the local primary care trusts, who fund services in different part of the UK, are also planning to jump to shorter durations of herceptin.

I think that the evidence is mounting that herceptin given only during chemo can really work well, although the existing trials are too small. There is the Hurley et al. 2006 study, with its impressive 4-year progression-free survival (PFS) rate of 81% for women with locally-advanced cancer, but it has no control group for comparison and involved just 48 patients:
http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum
It also includes adriamycin, which I think makes it less than ideal.

There is, of course, the recent MD Anderson study with its fantastic 100% disease free survival rate among the treatment group, but only 42 women participated in that trial, although it did at least reach statistical significance. It does at least include FEC, which makes it very useful for UK purposes. http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

Combining herceptin with an anthracycline seems a bit risky, but I know that women in the UK seem to be getting herceptin with epirubicin, although I can't find the trial that demonstrates the safety of this use (although the MD Anderson trial found no new problems).

So, I think for the UK at least, that there is a desperate need for trials that demonstrate better effectiveness and cost effectiveness.

Anyway, that's my two cents/pence worth.

Take care,

Christine

[Lani]

there was a study of the Pharmacokinetics of Herceptin authored mainly by researchers from Genentech showing that there was a 43% difference in how patients metabolized/excreted Hercepti and therefore how long it stayed active in the body. Genentech has no motivation to have patients tested to see if they are fast or slow metabolizers/excreters, but European governments do, if they will "step up to the plate" and do the studies themselves. Also, Herceptin vials need to be kept within a relatively narrow range of temperatures at all times--perhaps they could convince the manufacturer to put a smart RFID on each bottle to detect if it has ever gotten outside the range of safe temperatures. Should that be the case (and you know Europe and the UK lack adequate airconditioning!) it might be one reason for a less tha spectacular response to Herceptin.

Also, if some of these tumors are ER+ (45% of her2+ tumors are thought to be) it is quite likely these European patients are on tamoxifen and once patients are on tamoxifen only once the Herceptin is over, resistance can (and in fact is expected to) develop if the Herceptin and chemo were not sufficient to rid the bone marrow of the slowly dividing breast cancer stem cells. Whether the tumors will also develop resistance to AIs (and when) when given without herceptin is still also being determined.

Perhaps the longer course of Herceptin allows herceptin resisitance to develop and only shows up later and the shorter course would be better.

There is so much to find out and once Tykerb is approved it may confuse things as few will want to get less than state of the art treatment in one arm of a clinical trial.

Just my two cents worth for the moment...

[Christine MH-UK]

I just wanted to point out that the BBC article could give the misleading impression that the followup at this point had strengthened the case for the NHS to use herceptin as a single agent.

Cancer Research UK is doing a shadow study to determine the characteristics of patients for whom herceptin by itself makes a difference. In the Lancet article there seemed to be even fewer differences between subgroups than in the one year followup. The one thing that still stands out is that grade 2s have a much bigger reduction in risk than grade 3s (54% versus 27%), although in both cases the difference is statistically significant.

It could very well be, of course, that herceptin makes the biggest difference later on, since chemo takes out the faster cells but doesn't do much against the slower cells.

I would hope that the pharmacists would have the sense to keep the herceptin at the right temperature, although some indication of when the medicine had gotten too warm would be good.

My problem is not with herceptin and a 36% difference is still solid, but just that the reduction in proven cost effectiveness could mean some rocky times ahead for patients, since some local primary care trusts are really stingey with herceptin. UK oncologists do seem to be moving more to herceptin-based chemos for early breast cancer, even though these are not yet licensed regimes (although all of the medicines are, of course, licenced).

[Lani]

and having seen some of the old hospital buildings still in use and realiziing how few buildings are airconditioned I developed my worries.
I would think the Herceptin is kept refrigerated and delivered in refrigerated trucks and/or in styrofoam containers with ice as it is in the rest of the world , but was concerned what happened after the herceptin was mixed.

I think you made your point exceedingly well regarding the bean-counters and what they define as cost-effective, not taking the human suffering into account. Economists like to utilize cost-benefit analysis but if they truly did so they must put into the accounting the household help that would need to be hired for any children for household cleaning (God knows men tend to be rather useless in this regard) if the patient died, the time lost from work of the husband, the loss to the labor force if the woman worked.

GDP (a measure of all the goods and services produced and traded by a country) neglects the value of mothers' milk and housework, neither of which are charged for by most women.

A recent (published within the past week) paper on the amount of time taken off from work by those treated for cancer already showed a large financial (detrimental) impact on society.

And it is important to remember that the treatment of each patient allows lessons to be learned (even without formal participation in a clinical trial and even if only for one treating oncologist) about what worked/what didn't which advances the fight against the disease.

Are the local trusts made up of elected or appointed individuals. Maybe some should be selected who lost their mothers early in their lives!

[Christine MH-UK]

I know the private nurse who gave me my herceptin at home for the first four months I was on it was well aware that the herceptin needed to be kept cold. I can't speak for how things are done throughout the NHS, but at the NHS hospital the treatments seemed to be kept down in the pharmacy until patient/space was available.

One thing that needs to be kept in mind is that the HERA trial was rather different from in the US. For one thing, the European standard when HERA was done was FEC, which a recent Canadian studied showed was much more effective than the 3 weekly AC followed by 3 weekly taxol regime used in the US studies. For another, the herceptin was not given with the chemo.

I do think that more all-encompassing standards of the value of a human life need to be taken into account. The question is who will pay the bill (and I wouldn't want the really cost effective stuff like diabetes care or maternity care should get squeezed).

It is true that the time costs of cancer treatment are considerable, but isn't that one of the key reasons why shorter herceptin treatments are needed? As someone with a small child and a demanding salaried job, I really struggled with all the appointments. Not to mention that the MUGAs meant that I had to run away from my child at times because I was too radioactive (not pleasant). And then there was the herceptin-related fatigue, which did not make me the best of mothers at times.

[Lani]

All points well taken! By the way, couldn't you find a hospital who would do cardiac echos instead of MUGAs --they are widely used (at least in teaching hospitals with good equipment) instead of MUGAs in order to avoid the radioactivity.

I know some things just seem to be geographic!