Not impressed by BBC herceptin article

Not impressed by BBC herceptin article

Not impressed by BBC herceptin article My husband drew my attention to the article ‘Herceptin “shown to save lives”’ on the BBC website:

news.bbc.co.uk/1/hi/health/6230679.stm

and I think it gives the misleading impression that this study has strengthened the case for herceptin’s effectiveness. I have read the Lancet article and the accompanying Lancet editorial and this is simply not the case. Fortunately, there is good her2 news from other quarters including the first trial I have seen where noone in the control group recurred (better yet, using only drugs already available to breast cancer patients in the UK!). I just bring this up because the herceptin issue may hot up again.

Part of the reason I looked at the BBC story 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. Now a 36% reduction is still great for a cancer treatment; however, because giving herceptin only after chemo seems to be less effective that formerly believed, it is also less cost effective. The health economists who judged it to be cost effective (at £18,500 per quality adjusted life year or QALY) for NICE note that it is now out of the range where it is unquestionably cost effective (i.e. each QALY 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, big trials with better reductions in recurrence with longer followup, but the problem is that all of the really big US ones cannot be considered because control treatments included adriamycin, an anthracycline that is not common here in the UK, where the standard is epirubicin. A recent Canadian study demonstrated that the standard UK treatment of FEC (containing epirubicin) was much more effective than AC- taxol, so this seems to have been a solid decision on the part of NICE.

The Lancet editorial mentions the FinHer trial, a small Finnish trial, that is more 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 of herceptin in early-stage breast cancer).

Rather chillingly, the editorial mentions that New Zealand has turned down the full year of 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 remember reading somewhere on this forum or on the other site that some of the local primary care trusts are also planning to jump to shorter durations of herceptin.

There are some recent, small US trials that offer hope for both patients and the NHS. Hurley et al. 2006 study had an 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. The title of this article is “Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer” and the abstract is available through pubmed:
ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
The Hurley et. al regime also includes adriamycin, which I think makes it less than ideal, although the rate of cardiotoxicity was reasonable (just one case of congestive heart failure among the 48 women).

Most recently MD Anderson has announced the results of a trial with a fantastic 100% disease free survival rate among the treatment group at 16.3 months followup. The combination was 4*(taxol+herceptin) followed by 4*(epirubicin + herceptin). There were only 24 weeks of herceptin in this one, so the cost accountants will be happy if it works out in the long term. Only 42 women participated in that trial, although it did at least reach statistical significance. However, as I recall one of the reasons that this trial was so small was that they tried the treatment out as a neoadjuvant chemo and found that the response rates were so much better in the treatment group that they decided it was unethical to enrol more women into the control group than they needed to demonstrate statistical significance. They gave all the other women who had volunteered to be in the trial the trial treatment. According to the abstract, no new cardio problems were found, although it should be kept in mind that the cardiotoxicity rates in the US trials that might be used as a comparison were quite high.

So, the BBC story really got it wrong about the followup of the HERA trial strengthening the case for the NHS offering herceptin. Herceptin is still highly effective on its own, but questionably cost effective on its own. All is not lost, but the real hope is elsewhere.

you’ve said what I felt… Hello Christine,

I totally agree with your thoughts on the Lancet article / BBC coverage - but had wondered if I was just reading things wrongly. The Lancet and BBC both seem to now be pushing the overall survival benefit in the short term rather than longer term disease fee survival. It certainly looks like Herceptin is of most benefit early on after treatment - perhaps when recurrence at highest risk? - but that benefit lessens after this. Didn’t seem much difference between treatment and control group on local recurrence / cancer in other breast. I felt pretty disheartened by this - especially as Juliet has her last Herceptin on Thursday and it feels like we are off into the unkown again. I’ve not told Juliet about my concerns. She did rea the article but ‘chose’ to concentrate on positive - including comment that only Tamoxifen, of other BC drugs, showed same early survival benefit. Which reminds me that we need to speak to oncologist about whether Juliet should switch from Tamoxifen to Arimidex.

Anyway, thanks for the really helpful digest of the article - and other herceptin news - Christine.

Best wishes,

Sharon

Christine my onc [who I neither like nor have faith in] swears by Herceptin WITH additional chemo- and online figures confirm this.
H is shockingly expensive but probably a good investment for young HER2 br ca victims- plus even though it might not be the miracle cure we all long for it may well lead to longer [and we hope longer still] survival rates.
Some of these new bio chemos will turn out to be steps on the way to much better things for ladies and therefore a wiser investment than they look now.
Hope and better prognoses for ladies are costly short term but longterm really worth paying for. dilly

Yes great summary Thanks Christine,

Really interesting summary of the current position. I’m going to post a link to this post on the other site.

best wishes

Jane

Thanks from me too Can I add my thanks for a thoughtful and comprehensive review. Unfortunately i don’t seem to be able to access the ‘other’ site (I can’t get my Yahoo account to work) so I am grateful for the chance to read the discussions on this site - please don’t abandon it - buttons or no buttons!

Regards

Blondie

For SharonC It should be kept in mind that herceptin still cut recurrence by a third, which is excellent. The problem is more that the price is somewhat out of line with the effectiveness of this use as demonstrated so far.

I say as demonstrated so far because noone knows what will happen in future. Chemo tends to be especially good at knocking out the more aggressive cells, but not so good at getting at the slower cells, such as cancerous stem cells or slower cancers, things that are more likely to cause later recurrences. Herceptin has been shown to kill off her2 positive breast cancer stem cells in the test tube, so perhaps the long-term difference will be bigger than a third.

Personally, I am very impressed that the recurrences for women with more than four nodes have been reduced by a third. I think that that is a very good sign because this is the group that is most likely to have a very early recurrence and alot of chemo regimes aren’t particularly effective with this group.

It is also still early days. A comparison with radiotherapy may be useful here. I remember reading a health economics textbook written in the late 1990s that stated that with breast cancer radiotherapy the side effects generally outweighed the benefits, but later research has proven this wrong because: 1) more targeted uses of radiotherapy have been found and 2) the major benefits of radiotherapy largely show up in the second decade after treatment and the older studies were basing their assumptions on what happens in the first five years. It will probably take a decade for the full impact of herceptin to become clear.

So, I think that it is still early days for herceptin, but I also know that herceptin has its critics and think that it is a good idea for breast cancer patients to know the whole story. Otherwise we just seem like pawns of the drugs companies. (It might also be good for the drugs companies to learn this as well).

Just noticed a small error Of course, in my original post I should have said that noone in the treatment group of the MD Anderson study had died at 16.3 months followup. Not only that, there were no recurrences by that time either. Three people in the control group had recurred by that point, about 15% of the sample.

Really interesting.

Oncology at my hospital said there are moves to make Herceptin 6 months instead of 12 months, eventually…

I’d be interested to know which trial produced 100% survival so far so that I can read up some more. However long this result is over it’s a big step forward.

If only the Finher trial had been in higher numbers.

Steph x

Thanks Christine! Thanks so much Christine for such well informed and comprehensive posts on the H debate.

Thanks Christine… For putting my negative thoughts in persepctive. I was particularly taken with the possibility of differences in reurrences being more than a third in the long term…had assumed the difference would just get less as timne went on (not that I would want anyone to have a recurrence of course).

Another question - though I’ll put it as a separate thread too. Is it standard to have 17 or 18 Herpcetin sessions? I’m sure I’ve heard both mentioned. I’m sure that one of the oncs told us it would be 17 - but Juliet has just been for that one and we were told still one to go. Not the end of the world either way but, since we are still paying for the treatment, would be nice if we could discuss the posibility of dropping last one with the doctors. Of course, if it is clinically important to have 18 then we’ll go for it. If it is just local practice we might argue it a bit more…

Best wishes,

Sharon