An article by Lynda Williams of the Auckland Women’s Health Council lays out facts that may have been overlooked in this fraught debate.
At the beginning of the year another round of public controversy hit the headlines when Pharmac [the NZ government's pharmaceutical management agency ] announced it was considering funding a nine-week course of the breast cancer drug Herceptin for women with Her2 positive early stage breast cancer. Once again the facts were obscured by reporters, clinicians and lobbyists who were quick to voice their condemnation of the decision to fund a nine-week course of the drug rather than the 52-weeks recommended by the Herceptin manufacturer Roche. The managing director of Roche NZ, Svend Petersen, said he was going to seek an urgent meeting with Health Minister Pete Hodgson in an attempt to get the decision over-turned, stating “this has the potential to be this Labour government’s unfortunate experiment.” The truth is far less clear-cut than the news media and the pharmaceutical giant Roche are prepared to admit.
The Herceptin drug trials
Out of a total of 13,609 patients who have been involved in eight clinical trials regarding the anti-cancer drug Trastuzumab (otherwise known as Herceptin), 8,724 were treated with Herceptin. Of these just under half were given the drug after their chemotherapy treatment (sequentially), and just over half received the drug during their chemotherapy (concurrently). The difference between these two groups is very important, because the data reported so far from the eight studies have revealed that sequential treatment is significantly less effective than concurrent treatment, although the latter carries greater risks of toxicity including damage to the heart.
Sequential Herceptin studies
There are two large studies on the effectiveness of 12 months treatment with Herceptin after chemotherapy. One study of 1694 patients (HERA/1 year) showed some benefit, the other study involving 985 patients (N9831 arm B) did not. A third study involving 1694 patients (HERA/2 year) has yet to be reported, and another study (N9831 arm A) is missing. Roche has said it is unable to supply the full data for the missing arm of N9831. This is a significant and worrying issue given the amount of money involved and the need for full disclosure by drug companies of all the results of drug trials.
Concurrent Herceptin studies
There have been five studies on the effectiveness of Herceptin given concurrently with chemotherapy. Three of these involved 52 weeks of concurrent treatment with Herceptin, one of which is a study of 840 patients (N9831 arm C), a fourth study (FinHer) involved 9 weeks of concurrent treatment with Herceptin, and the fifth study (Sledge) involved a comparison of 52 weeks with 10 weeks of concurrent treatment with Herceptin.
FinHer study
The data on the 116 patients in the FinHer study is for 3 years of follow-up and reveals that short duration concurrent treatment with Herceptin is effective at preventing recurrence of disease. In
Finland both the 52-week course of concurrent treatment with Herceptin and the 9-week course are available to women. However Finnish doctors prefer the 9-week course because there is less likelihood of cardiac damage and because the doctors were involved in the FinHer trial and saw for themselves the benefits to their patients of the 9-week course. This experience makes a big difference when doctors are making recommendations to their patients on best treatment options.
Sledge study
The data on the 227 patients in the Sledge study is for 5 years of follow-up and it showed no difference in survival rates between those who received 10 weeks of concurrent treatment with Herceptin and those who received it concurrently for 52 weeks. It is obvious that the issue of concurrent treatment with Herceptin versus sequential treatment is at the core of this debate. The results of these studies revealed that concurrent treatment with Herceptin results in significantly better efficacy than sequential treatment with the drug, all of which casts grave doubts on the superiority of the sequential treatment regimen being promoted by Roche. The pharmaceutical industry is an extremely powerful lobby group that has a vested interest in the outcome of drugs they produce and market. As a recent article in the Sunday Star Times revealed, the reason other countries have not opted for the 9-week course of Herceptin is because in places like Britain it is the drug manufacturer who decides what treatment period they will request for their new drug, and of course in the case of Herceptin, Roche put forward the more expensive 52-week course of treatment. The international trials just described have raised important questions about the optimum duration and sequencing of Herceptin treatment. A further trial is being planned to find the answers. It will be headed by Professor Heikke Joensuu of the University of Helsinki in Finland, who headed the FinHer trial and who has extensive international experience in trial design and management. Roche of course is not interested in funding further 9-week trials of Herceptin. The interests and position of drug companies around issues such as research choices, length of treatment and treatment sequencing, not to mention pricing, do not always align with the public interest or even patient safety. The promotion and marketing in
New Zealand during the 1970s of fenoterol for asthma, and HRT during the 1980s for women during the menopause are powerful evidence of that. Meanwhile Pharmac has indicated funding support of NZ$3.2 million should the trial proceed.
New Zealand’s participation depends on Herceptin funding decisions and on support from
New Zealand oncologists to recruit patients to the study. Roche of course will be doing all it can to ensure that other countries don’t follow suit. Auckland Women’s Health Council Newsletter March 2007
For me this as a woman in her 4o’s with HER2 early breast cancer this is an is an interesting article. I agree with many of the coments made here and have decided despite having funding available for 52 weeks of herceptin to go with the NZ regime of nine weeks concurrent treatment. I have done this on the basis of evidence I have read and my instincts as a health professional. However I feel that even your article may be slightly misleading. You do not state whether The sledge study was carried out on women with HER2 early breast cancer or secondary cancer and this is very relevant to the whole debate surely? I would be interested in your comments.
Kind regards
Karen Richards
had 13/17 scheduled Herceptin (first four with other chemo)heart muga test have went from 70 (pre-herceptin) to 57 to 48 yet doctor still has me on chemo just did forth muga. (they said if below 45 they will not give me any more; already have heart and chest pains- can barely walk without getting tired). Worried (single parent) should I demand to be treatments to stop? I live in Canada
Thank You
I have forwarded both your comments and questions to the author of the article.
I recommend trying this: adding CoQ10 supplement daily to keep the heart functioning well while on Herceptin and after its conclusion. My wife’s LVEF dropped to 43% (from 55%) after 18 or 19 weekly treatments and was taken off of it. She started taking COQ10 100 MG’s daily and within about 3 1/2 months had rebounded to 55%–her original top rate. Seven months later her MUGA was 65% (she has been back on Herceptin , 11 in 12 weeks) and now taking 200 MG’s daily. Due for a MUGA again in about 6 weeks. So far no physical signs of lowered heart function, no tiredness or shortness of breath.
I have been put on herceptin almost one year prior to my chemo therepy. I will be going for my thir treatment and I already feel chest pains. I was FEC-D then rads. Then I found out I was her2 positive not triple negative as the hospital had lost a supplementary report. I’m wondering if the herceptin is worth it sequentially. I am so concerned about heart problems as my previous chemo was very aggresive and the radiation did hit my heart on the left side as well. I find out later that 9 weeks would have sufficed and the drug company covered it up I will begin a mass law suit (if) I get a heart condition. There is so much we don’t know but I can see the drug companies pushing for 52 weeks of treatment thats alot of coin going to them and I hope it’s not at the cost of my heart.
Hello Gillian,
As a former patient who has followed the herceptin trials from the beginning, I really enjoyed seeing this.
The big question I have about FinHer is why is a trial that showed excellent results at St. Gallen in spring 2009 struggling so much. O.K., a ‘patient group’ seems to have driven it out of New Zealand, but I notice that it now no longer seems to be recruiting in the UK either and, because it is having to rely on Finnish recruitment the completion date has now been pushed back to 2015. Admittedly the initial trial was a small trial, but that only 9% of the women treated developed distant recurrences at the five year mark is impressive. Hurley et al. also had very good results with similar study of extremely high-risk patients in Florida.
I have noticed some really odd attacks on FinHer in strange places (like in U.S. newspapers, which I didn’t know cared that much about small trials in Scandanavia and New Zealand), which makes me suspicious.
You might have also mentioned that Genentech/Roche have not been particularly good at full disclosure on their trials, such as not releasing the 2 year arm results of HERA.
Sorry, I phrased that last bit wrong. It is just that HERA/2 year has yet to be reported: the scientists have repeatedly promised to report it over the past four years at specific conferences and oddly pulled out each time.
as an early her2 patient in nz i am presently in 9 wk programme recommended by finns. having attended business school and up front experienced the incredibly galling lack of concern for patient outcomes over profits with the big pharm co’s and in contrast the thoroughness and creativity of the finns in professional capacity i am keen on the finnish program. then again, its amazing how much confusion there is amongst professionals. i can choose to extend the program. would really like to hear from people on the 9 week course and hear of their experience compared with longer-term course participants – we patients talk and what are 9 weekers thinking?