Hello Christine,
I saw your posting under the ‘is herceptin worth it’ thread. So glad you are well. It is the fourth anniversary of Juliet’s diagnosis today - bringing up very mixed feelings , but she is currently (fingers crossed) NED.
Wondered if you knew if there has been any further follow up on the Hera trial. Last I remember was 2006…I’ve looked at the ASCO site but don’t find it particularly informative.
With all best wishes,
Sharon
Hi Sharon,
It is really disappointing that the HERA followup hasn’t been better. However, I remember seeing an item a few years back indicating that the lion’s share of her2 positive relapses occurred in the first two years and that the HERA reductions in recurrence remained substantial, although a 38% reduction in recurrence versus the 50% originally reported. Nothing has ever been reported on the two year tail, which suggests that there wasn’t a sufficient benefit to report the results out.
A quick check of the literature (thank heavens for Pubmed), indicates that European health economists now consider the the single year of herceptin to be cost effective, so we have been vindicated in pushing the NHS to use this drug.
I expect that the lack of followup may reflect that HERA is being replaced by other uses. Herceptin seems to be more effective when combined with other drugs than when it is used on its own, so interest has shifted towards combining herceptin with other drugs to make it more effective. Second, the full year is quite costly, so there is greater interest in shorter trials, with calls for a Finnish trial that used just nine weeks of herceptin-based chemo after FEC to be repeated on a larger scale because the results were quite possibly better than HERA’s. For a long time it seemed like it was just me blathering on about FinHer, but now it is the health economists doing it, so something might get done. I doubt that they bother reading the posts of breast cancer patients, but I am proud that most of what I said years ago is what the professionals seem to be saying now. Just in case any health care economists are reading this, please look in Pubmed at Hurley’s 2006 “Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer,” which seems to be incredibly promising in stage III patients, with relative safety and cost effectiveness. I have lost too many stage III computer buddies. I have brought this to the attention of my oncologist, so maybe he is doing something.
I am glad that Juliet continues to do well.
Hi Christine,
Thanks for this information. I was just wondering though, when you say within the first 2 years is that 2 years from the date of diagnosis or 2 years on finishing Herceptin? Or maybe it is something else!
Pauline
Thanks Christine. Seems likely, as you say, that HERA is less relevent now that there have been other trials -and glad that FinHer still looking good. Pauline -I think it is 2 years after diagnosis, though Chrstine will know better than me. I went to the NICE review on herceptin and oncologists there were saying that getting past the first 2 years with no recurrence was significant. This was in the context of a cut off period for offerring the treatment…ie that Her2+ people who were already two years post-diagnosis with no sign of cancer might have a lower risk and not need herceptin. One reason I’d like to see continued follow up on HERA is to see whether there is any evidence that herceptin just postpones a recurrence or whether it can do better than that. Might not know that properly for years though…
Best wishes,
Sharon
Hi Sharon,
I would like to know that as well. Unfortunately, there seems to be a pattern on HERA of them saying that new results will come out at San Antonio in December or ASCO in June, but not delivering. There has been speculation that if the two-year arm results turned out not to be better than the one-year arm then it would raise questions about the need for even one year of herceptin, so the corporate backers have a motivation not to announce results (since people would ask about that arm). Or it may be that the results are a bit dull and conferences and journals don’t like dull stories. Herceptin can kill off those evil stem cells, at least in the test tube, so there is the possibility that the effect will last.
FinHer is going forward as the SOLD trial, which includes at the very least Finland and New Zealand. New Zealand adopted FinHer (even though the trial was rather small scale) because the health system can’t afford the whole year and they weren’t sure that the full year was any better than FinHer. If you feel in a technical mood, the full rationale is laid out at: nzma.org.nz/journal/120-1256/2593/. I am very glad that they are doing a trial, partly because the word has gotten out that nine weeks of herceptin worked in a trial and some oncs, mainly in the U.S., have misunderstood this to mean that nine weeks of herceptin alone after chemo works, which isn’t at all what FinHer said. This is not a UK problem; it is more of a U.S. one (I am guessing uninsured or underinsured rural Americans who don’t get a proper breast cancer oncologist and can’t afford the full year, which is even more expensive in the States).
The figures refer to two years after finishing treatment.
Hi Sharon,
Another thought: the long-term follow up of HERA is problematic because they gave the control group herceptin if they remained recurrence-free when the trial results were announced. As such, there is really no good group to compared the HERA treatment group against.
I always enjoy reading your comments Christine, because you appear to have such a good grasp of the issues involved. I hope you don’t mind a dumb question here!!
Prior to moving my treatment to the Marsden, I was set to participate in the Persephone Trial which was comparing 6 months of herceptin against a year and used the FinHer Study as an example. Now here’s the dumb bit (and this dumb bit kept on nudging me when I tried to understand the implications of the FinHer Study) what do we mean by 9 weeks treatment alone? My participation in the Persephone Trial had I not moved would have meant finishing chemo and starting herceptin with a gap in between - one treatment following another. Did the FinHer Study rely on chemo and herceptin being delivered together?
Please forgive my ignorance if you consider this a silly question!
Gill
Hi Gillian,
Not a dumb question at all! FinHer was nine weeks of herceptin and taxotere followed by nine weeks of FEC.
I think the thing to keep in mind regarding the Persephone trial was that the earlier trials decided on a year of herceptin based on experiments in mice. More recently, they have given women herceptin neo-adjuvantly (before chemo) and found it to be more effective at reducing tumours than they had expected, so there are really questions about the optimal length. I think that a year is not ideal for patients because in my experience, it is the final six months when the side effects really kick in. In fact, I have heard of patients getting so worn down in the last few months of herceptin that they lose their jobs (mainly in the U.S. where the employment protections for cancer patients aren’t very good).
The risks of combining herceptin and chemo are a higher incidence of heart problems. This problem definitely arises if the herceptin-based chemo is used after anthracyclines (AC or FEC followed by herceptin + taxane, for example). FinHer is nine weeks herceptin + taxane followed by FEC on its own and seemed not to have the heart problems. It was a fairly small study, though, so the SOLD trial will have to check out its heart effects further. The really promising trial I mentioned above was even smaller, with good early heart results, but lousy lousy followup due to uncooperative patients. The fellow who invented herceptin has always seen it as being primarily a chemo-sensitizer, so if he is right SOLD should be the way to go, although we will have to see what the heart effects are.
I will be taking a break from the board for a few weeks (resting up a bit before the San Antonio Breast Cancer Symposium).
Christine,
Very interested to read your comments about the side effects kicking in for the final six months. I started herceptin last November, naturally not feeling too good after surgery/chemo/rads. But as time went on I started to feel much better - I remember being aware of having much more energy in June & July. But since August I feel that I have been slowly going downhill, and I am getting more & more tired. I can track it in my running times - I am back to where I was a year ago, which was dreadful, being only two months on from tax. I was running really well in the summer, and now I am slower every time I go out. It is very demoralising. I could not understand why I was feeling like this when I had felt so well in the summer. Perhaps this explains it. I have one more treatment to go, then hopefully I can expect to improve.
Christine, thanks for explaining that so clearly. I can definitely see why SOLD could be the way to go. That makes a lot of sense to me. Interesting in relation to the Persephone Trial that we’re testing Herceptin delivered very differently to the methods used in the FinHer study. I so hope that we eventually reduce the level of treatment.
RoadRunner - it does sound like this is likely to be the herceptin. I’ve only just begun - have my second dose tomorrow. So far I’ve been feeling great but will now be more prepared for the final slog of the treatment!
Enjoy your break from the board Christine and I hope the San Antonio Breast Cancer Synopsium provides stacks of interest!
Gill
Story title “Herceptin proven to benefit women with HER2 positive early breast cancer – latest results from the HERA study”
At four years of followup, the reduction of risk of recurrence on the HERA trial is down to 25%. At this point, here is only .01% of a chance that herceptin doesn’t make a difference when given after chemo in this very large study. Cardiotoxicity associated with herceptin used sequentially remains low: .08% Disease free survival was 79% in the treatment group.
Story title: “Short Course of Adjuvant Trastuzumab With Chemotherapy Has Good Long-Term Safety and Efficacy for HER2-Positive Breast Cancer: Presented at SGOC”
In the much smaller Finher (232 women in the her2 positive subset), the rate of distant mets at five years followup declined 68% with the addition of herceptin to taxotere before FEC and there is less than 3% chance that the effect seen is down to chance. Only 9.3% of Finher patients have had distant recurrence. Only 1 person developed cardiotoxicity in the herceptin group compared with 2 in the control group.
The risk of death declined 58% in the smaller Finher trial. It was impossible from the abstract provided to judge whether the trial had proven that herceptin significantly improves overall survival, so it probably has not met that end point (the only downside to women living a long time with her2-positive secondaries). The HERA trial says absolutely nothing about the updated trends in overall survival, but things may have been messed up by the humanitarian decision to give the disease-free members of the control groups herceptin.
Personally, I think that it is probably unfortunate that Finher was such a small trial, even though herceptin after chemo clearly makes some difference. It is possible to make a statistical case with the lowish numbers that Finher has, but the impact needs to be much bigger to do so because of the larger margin of error. Although I think that New Zealand jumped the gun with its move to test the FinHer regime in the SOLD trial, this new information seems to indicate that running a HERA treatment against FINHER is not a stupid or irresponsible thing to do with hindsight. Rather strangely, though, the attacks on Finher and New Zealand’s trialling of it seem to have mounted recently in the blogoshere.
Hi,
I was diagnosed 4wks ago and have already had WLE with clear nodes and magins and Her2+. I live in Glasgow and have just been offered the SOLD trial. It started here this week. needless to say being a newbie I have no clue as to what all this is about and my initial panic was “oh God, what do I do?” I am currently trawling the site and this is the first reference I have found on SOLD… I had already gethered that mixing tax with herceptin was very promising, and now feel a lot more positive about the trial. I have 2 weeks to make up my mind. If anyone has anymore info please let me know.
Thanks
Fiona X
Hi Fiona,
You might see what your oncologist knows about the St Gallen presentation of the FinHer data. It looks very promising, but it is always better to ask an expert.
SOLD and Finher don’t get much neutral publicity. There is no big corporate PR department behind Finher and I think that the news around it has suffered somewhat. Certainly the abstracts are much harder to decipher. This is one of the reasons I have followed this trial fairly closely and disseminated its results as impartially as I can.
I realised later that I misinterpreted one of the stats incorrectly. The incidence of distant disease was halved in women who got the herceptin at the five-year follow up point, which is still very good, considering that the rate has held up for five years. The higher figure of 68% was the increase in “distant disease free survival.”
I think that there might be real advantages to patients from the SOLD trial. If the taxane and herceptin are given before the anthracycline, there is no danger of a patient not qualifying for herceptin because of anthracycline-induced heart damage, as sometimes happens. The treatment time is shorter as well, which I think helps recovery.
You have to be a bit careful in assessing this trial because I have noticed a number of bizarre attacks on Finher lately, basically saying that it was a bad thing because it only used nine weeks of herceptin. Admittedly, New Zealand probably did adopt it on cost grounds, but the five year results, including the big improvement in the risk of death, look good. The trial raises the question of whether patients who have gotten herceptin-based chemo really need to spend the rest of the year on herceptin. Needless to say, there are some very serious financial interests at stake.
I should also add that if I were in your position, I would go for the trial. I had 6 * FEC pre-surgery, 4 * taxotere post-surgery and a year of herceptin after chemo and I am still here despite being my oncologist’s highest-risk her2-positive patient (he let this slip once), even though FEC didn’t do much for me.
You should consider what your treatment would be like if you don’t have the trial. The standard for a node-negative, hormone-negative patient would be herceptin after chemo, but that is probably not as good as herceptin-based chemo. Herceptin-based chemo is not usually used for node-negative patients in general because all of the big trials used herceptin-based chemo after anthracyclines and had problems with heart failure that made it too risky for lower risk patients. FinHer seemed to crack this problem by changing the order of treatment (google “Avoid Herceptin cardiotoxicity: Give it before anthracyclines” for more on this). Some trusts also will not spring for taxanes for node-negative patients.
Just a quick comment: I said below that ‘all of the big trials used herceptin-based chemo after anthracyclines’ and remembered that this is not correct. There was a big trial that didn’t use anthracyclines: it used herceptin, carboplatin and taxotere followed by the remainder of the year on herceptin with survival results that were comparable to the other big trials. However, as far as I can tell, this trial has had absolutely no influence in Britain. I am not sure why. Carboplatin is off patent and sometimes used on BC patients, so I don’t think the issue is price. Are oncologists perhaps reluctant to stop using anthracyclines or do they dislike carboplatin for some reason? I don’t know, although HCT now seems to be much more commonly used in the U.S.
I think SOLD is important because, if the heart results hold up, it would provide a way to use anthracyclines and herceptin in a way that gives patients the survival benefits of herceptin-based chemo without the heart risks found in most trials.
Dear Christine,
Thanks for all your information. This definately gives me more insight into the trial. I am feeling quite positive about the trial at this stage. I will of course be discussing the information with my oncologist next week.
Thanks Again
Fiona x
I found the original abstracts for FinHer (very information) and HERA (not very informative) at oncoconferences.ch/index.html.
The FinHer abstract says: “Only 5 (9.3%) patients treated with docetaxel, FEC and trastuzumab were diagnosed with distant metastases or died without cancer recurrence as compared to 15 (25.9%) patients treated with docetaxel and FEC without trastuzumab.” Unfortunately,with such small number it is hard to reach statistical significance, so it could be a fluke, but the increase disease free survival is probably not.
Dear Christine,
Once again Thankyou for this. I have found it very informative.
Regards
Fiona xx