Herceptin More than 12 Months Out Revisited

I recently posted a question about Herceptin for those of us more than 12 months out of treatment and who are NED. I appreciate the great responses.

My background: diagnosed 9/03, 4 nodes +, ER+/PR+, Her2 +++, 6 cycles CAF completed 4/04, radiation completed 7/04, Walter Reed vaccine therapy graduate, arimidex (after ovary removal).

I just had a PET/CT scan this week and all is well.

I have received two entirely different opinions from two oncologists I consulted about getting Herceptin at this stage of the game. Hence, I would like any input you may have to offer

Onc. #1: Don't do it. She said that the trial showed a great benefit for Herceptin in combination with Taxol (approx. 56%), but less of a benefit (approx. 14%) when given after Taxol. Given that I didn't have Taxol at all, and that I am so far out of chemo, there is no evidence how Herceptin would work. (Christine, you have said that the HERA trial showed the best benefit is for those who received a CAF type regiment -- I would love to see what is written on that so I can show it to this onc.) She said that the heart problem rate in the trial was 4%, whereas it is nowhere near that high for mets patients. I asked why and she said they don't know though they think it may have to do with the closer proximity of Herceptin and Adriamycin used in the early stage trial). Bottom line, she said you have to do a risk v. benefit analysis. She said that if you compare a 4% heart risk against a wholly unknown benefit that is probably 14% at best, it makes little sense to proceed. Also, because I am this far out from chemo with the statistics in my favor of being NED, why risk that level of heart harm when there is a good chance I am cured. She said that if the treatments were successful (big IF), there is no cancer left and thus nothing for the Herceptin to do other than possibly damage my heart.

Onc. #2: Go for it. He said that since there is a clinical benefit for those who did receive Herceptin according to protocol, he believes, in the absence of data, that I may well get some benefit even one year out. Thus, he is willing to give it to.

So here is the quandry: Is it reckless to pump drugs into us never been Herceptin studied gals without any actual data of benefit but with known data of a potentially lethal heart risk.

I know that this is an issue of great concern to many of us, so I would greatly appreciate your input and a report on what you are hearing from your oncologists and others.

Thank you so very much,

Cynthia

I am receiving my second Herceptin tomorrow (but I am 4 months out of chemo and did receive Taxol). The Hera study isn't over (comparing Herceptin after Taxol for 1 year versus 2 years). The 1 year data shows about a 14% benefit over taxol alone but it is not complete and does not show a recurrence survival rate that is out there for 5 years (or what the 10 yr rate will be which could be much, much greater).

I went to Sloan Kettering as a second opinion just for that same 14% you are asking about. The onco there told me, "it may not seem like much but it is preliminary data. All the facts won't be in for quite some time". Secondly, she told me that some facts on using Herceptin for 2 years will be out soon (next few months) and that may greatly benefit folks (especially if you are taking Herceptin for one year and aren't done yet but they find that 2 years is fantastic).

You need to make your own decision but I am willing to try anything to prevent a recurrence and if I do have one in the future, I won't have any "what ifs" or regrets.

God speed

Becky

Just to clarify, since many still seem to be confused about this. It was the B-Arm of the N9831 trial that showed a 13-14% recurrance reduction for those receiving herceptin AFTER ACT vs. those who received ACT alone. The (international) HERA trial -- where patients receive herceptin for one or two years, or not at all, after ANY chemo combination (many received CEF, FEC, FAC, etc) -- showed a 46% reduction in recurrance between the treatment and observation arms. Please see the attached information: HERA press release from ROCHE

"Guest"

I appreciate your post and I am confused. Are you sayin that the HERA results showed a 46% response rate whereas the B arm of the N9831 trial showed a 14% response rate when Herceptin was received after ACT, thus showing a conflict in the two results? If so, has anyone been able to explain away such a dramatically different showing? I don't see any discussion of that in the article you posted.

Also, any explanation for the difference between the .5% heart problems cited in the HERA study vs. the 4% problem noted in the N9831 study (which are hugely different numbers in my mind)?

I greatly appreciate any input that people can offer. Back-up support is also very helpful as I (and I know many others who read this site) fully intend to gather together all applicable research in order to make a (hopefully) informed decision.

Thank you.

Cynthia

Hi Cynthia,

I, too, have wondered about these conflicting results and will be getting my onc's opinion on the subject next time I see her. I'm wondering if, as the HERA trial 'matures', their numbers will come down abit. Or. Could it be because many of the women in HERA had anthracycline-based treatments which have been shown to be beneficial in HER2 cancers? I appreciate that the US trials had adriamycin but the doses in AC are much lower (60mg/m2 X 4 treatments) vs., for example, FEC where the dose for the anthracycline epirubicin is 100mg/m2 X 6 treatments -- well over double the dose of an anthracycline drug!. Anyway. Just a theory. Just what I want to be true. ...I'm hanging on to that 46% and I'm not letting go! : )

Cheers,

/Christine

Dear Cynthia,

On the HERA trial, the risk reduction overall was 46%, but there is a chart in the presentation on slide 15 out of 21 that shows that the recurrence reduction after anthracyclines was 57% (1 - .43 (the hazard ratio)) , but the recurrence reduction after anthracyclines + taxanes was just 23% (1-.77) Whenever a line on the chart passes above the number one on the bottom of the chart, that means that the finding was not "statistically significant" for that group. In other words, there is more than a 5% chance that herceptin is not of benefit for that particular group. So, while it is true that both arm B of the U.S. trial and HERA found a reduction in risk when herceptin was given sequentially after an anthracycline/taxane combo, they weren't able to prove that this reduced risk wasn't just a fluke. For women who only received an anthracycline, however, the benefit of herceptin was clearly statistically significant. Just eyeballing it, I would say that the benefit is likely to be a risk reduction of at least 42%.

Of course, nobody knows that the risk reduction would be like for women who got the Walter Reed vaccine and also got herceptin.

I checked the heart risk for arm B and it was 2.2%. My best guess for the reason why HERA had fewer heart problems was that in some regions, like Europe, the anthracycline normally used is epirubicin rather than adriamycin, and epirubicin is much easier on the heart. In fact, M.D. Anderson did a very successful phase I trial of concurrent epirubicin and herceptin and didn't notice heart problems. So she's right that arm B's cardiotoxicity problems would be the ones that are relevant for you.

It would be interesting to see a combined analysis would yield (all of the anthracycline + taxane -> herceptins contrasted with anthracycline + taxane alone for arm B and HERA combined).

I need to talk to my oncologist about his reasoning for why I need herceptin, but I suspect in my case it may be that my cancer hardly responded to pre-surgery epirubicin (I had taxotere afterwards, so a non-standard combo) and that I had a very bad mix of risk factors, so any percentage improvement is important.

Best of luck,

Christine MH (not to be confused with the main Christine. I just try to keep the same username and password for all my cancer-related stuff)

Thanks, Christine MH, for your reply and for bringing my attention to the details of slide 15 -- not to mention the explanation of how to interpret that chart.

In another message on the same question you stated: "there was a study presented at ASCO which showed that six rounds of the anthracycline FEC resulted in a poor prognosis for HER2+, whereas 3 FECs followed by 3 taxoteres did not". I've been unable to find the specific abstract and wonder if you could provide a link...

Cheers,

Christine (Adams. In Vancouver.)

Maybe THIS is why I had 6 Taxotere, Epirubicin and Cytoxin (I've not seen ANYONE with this combination) and I am weakly her2.

As someone with bc who is also ER+ PR+ HER2+++ and who was treated with CAF x 6 and am more than 12 months out, I wonder what the best choices are too.

Since we have never had a taxane, I wonder mostly if we would get the greatest benefit from doing a taxane simultaneously with Herceptin for a dose or two, rather than doing say, Herceptin for a year or for the rest of our lives. Combination therapy is supposed to work better than just Herceptin, and doing a dose or two makes better sense economically as well. Since there is no data on this but there are an awful lot of us in the 12-month-plus group out here who either got CEF (FEC) or CAF (FAC) before the taxanes were as commonly used, I would think this would be a logical choice for oncologists to consider in doing a clinical trial.

The more high-risk factors you have, the more seriously you should consider Herceptin. You and I are high-risk because of being HER2+++ but we are at lower risk because we are steroid-receptor positive. However, node-positive also raises the risk in the same way that being ER/PR negative would raise the risk. I personally favor the most aggressive approach.

The farther out you get the better, but at the same time, the farther out you are the less this may end up being your choice to make until better clinical data is established.

So... for me there are 2 questions involved. Should anyone who has completed treatment without Herceptin or a taxane be treated with combination therapy rather than just Herceptin, and get just a few doses, or should we be treated with just Herceptin on a longer-term basis? The qusetion there is, would Herceptin long-term be worse on hearts that have already had either Adriamycin (docycycline) or epirubicin, or would a short run of combination therapy be worse?

Another alternative would be for you to ask an onc about having the Bayer Serum test (thanks Joe/Christine and StephN), to try to see if that helps indicate whether you are at more of a risk.

AlaskaAngel

Hi Christine Adams,

I got it from a web source that Joe mentioned a few weeks ago (somebody named Sheila had recommended).
HER-2 Overexpression, PR Negativity, and High Ki-67 Expression Predict Poor Response in Node-Positive Breast Cancer Patients
- A report on data presented at the conference
Retrospective analysis of the randomized, multicenter, phase 3 PACS 01 trial

The key points were that HER-2 overexpression, Progesterone receptor (PR) negativity, and high proliferation (Ki-67) were associated with a poor prognosis for patients receiving 6*FEC100, but "HER-2-positive status not a factor in poor prognosis for FEC100/docetaxel arm . HER-2 status may be useful predictor of benefit from sequential anthracycline/taxane chemotherapy"

I just also wanted to bring people's attention to the lack of statistically significant benefit for ER+ cancers, since that may be relevant when people make their decisions. People who are ER+ and got an anthracycline and a taxane may not get much of a benefit, but people who are ER- and got an anthracycline alone should definitely go for it if they can. I figure that being ER-,PR- it makes sense for me, despite having gotten a taxane because the options in case of a recurrence are so unattractive.