Latest Data from The HERA Study

[Joe]

Media Release


http://www.roche.com/media/media_releases/med-her2-200px.jpg Comparison between a HER2 positive and HER2 negative breast cancer
(http://www.roche.com/media/media_releases/med-her2-600px.jpg)
Basel, 11 March 2009
Herceptin proven to benefit women with HER2 positive early breast cancer – latest results from the HERA study

Study confirms Herceptin’s promise of extra years of living cancer free
The Breast International Group (BIG) in collaboration with Roche announced today that women with HER2 positive early breast cancer continue to benefit from Herceptin (trastuzumab) several years after treatment completion and as a result enjoy a longer life disease free. The patients were treated for one year with Herceptin and followed up for four years. These data from the HERA study were presented at the Primary Therapy in Early Breast Cancer conference in St. Gallen, Switzerland.
The HERA (HERceptin Adjuvant) study showed that women treated with Herceptin had a 25% reduction in the risk of their cancer coming back compared to women who did not receive Herceptin, and after four years of medical observation on average, almost 90% of the Herceptin-treated women were still alive. In addition to the significant treatment benefit, this analysis confirmed the long-term safety profile of Herceptin, with good cardiac safety and tolerability maintained throughout the four-year follow-up period.
“These data are extremely important for the treatment of breast cancer” commented Dr Martine Piccart, lead investigator of the HERA study and Chair of BIG. “HERA is the first of the four large Herceptin studies in early HER2 positive breast cancer to substantiate the long-term benefit derived from one year of treatment”.
“These important long-term results from the HERA trial reinforce that women with this aggressive type of cancer have the best chance of cure with Herceptin”, said William M. Burns, CEO of Roche’s Pharmaceuticals Division.
Historically, HER2 positive breast cancer has been associated with a poor prognosis, but the first analysis of the HERA trial, released in 2005, established unprecedented benefits in terms of lowering the risk of cancer returning (disease-free survival). “It is rewarding to see that women with HER- 2 positive early breast cancer can be confident about their future with Herceptin as the foundation of their treatment” said Dr Luca Gianni from the Istituto Nazionale Tumori Milano, Italy, lead investigator of the HERA study.
To date, four large studies – HERA, NSABP B-31, NCCTG N9831 and BCIRG 006 – have consistently demonstrated that Herceptin prolongs survival in women with HER2 positive early breast cancer.
About the HERA study

HERA is a large international phase III study conducted as collaboration between BIG and Roche. The study, with over 5000 patients enrolled, is assessing the benefits of adjuvant Herceptin treatment in women with HER2 positive early breast cancer. The primary endpoint is disease-free survival (DFS), the secondary endpoint is overall survival (OS) and cardiac safety.
Previously, with 2 years of median follow up, the HERA study demonstrated that one year of treatment with Herceptin given at three-weekly intervals after the completion of adjuvant chemotherapy and/or radiotherapy achieved a highly significant improvement in DFS versus the observation group (no Herceptin), reducing the relative risk of relapse by 36% (hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.54, 0.76; p=0.0001).1 Herceptin also reduced the risk of death by 34% compared to observation (HR: 0.66; 95% CI: 0.47, 0.91; p=0.0115). Upon publication of these unprecedented results in 2005, more than 50% of the patients in the observation arm opted to receive Herceptin (‘crossed-over’ to Herceptin treatment).
The focus of the current analysis was to evaluate the efficacy and safety of one year of Herceptin treatment versus no Herceptin at a median of four years follow-up after entry onto the study. The results of the analysis including all women involved in the trial (intent to treat, ITT) showed a 25% reduction in risk of cancer recurrence for women receiving Herceptin compared to those on observation (no Herceptin) (HR 0.76; p=0.0001). At four years of follow-up, nearly 79% of women receiving Herceptin remained cancer-free, a significant increase compared to 73% of women in the observation arm. With regard to safety, it was shown that the incidence of severe cardiac dysfunction associated with adjuvant Herceptin-based therapy was low (0.8%). These results confirm the benefit and safety of one year of Herceptin treatment in women with HER2 positive tumors despite the substantive crossover of patients from the observation group to active treatment. The present analysis also suggests that women who crossed over derived benefit from Herceptin even if they started Herceptin therapy late after completion of adjuvant chemotherapy.
The HERA study is ongoing and final results are expected in 2011.
About breast cancer

Breast cancer is the most common cancer among women worldwide.2 Each year more than one million new cases of breast cancer are diagnosed worldwide, and nearly 400,000 people will die of the disease annually.3
In HER2 positive breast cancer, increased quantities of the HER2 protein are present on the surface of the tumour cells. This is known as ‘HER2 positivity’ and affects approximately 20-25% of women with breast cancer.

[Christine MH-UK]

25% is something, but haven't the other trials that used chemo with herceptin had better results?

I just hope that the reduction risk doesn't get any lower. It was 50% in 2005, 33% a while back and now 25%. Also, no results from the two-year arm.

I am just a little downbeat about this because herceptin after chemo is still routinely used in the UK, even for high risk cases: the big international trials using AC->taxane as the control aren't considered to be relevant because AC->taxane isn't used very much in the UK. That is why HCT is not being used in Britain.

[Mary Jo]

Thank you Joe for submitting these results to our forum.

As a 3 1/2 year survivor (I was stage 2B) I am incredibly thankful to God - to Dr. Slamon and lastly (but CERTAINLY not least) to herceptin. A true life saver to many.

Thanks again Joe for all your efforts. You are appreciated.

God Bless you,

Mary Jo

[Becky]

Dear Christine (in the UK)

The results of the trials where Herceptin is used with chemo have very similar results over time as the Hera trial.

The last results I saw 18 months ago also reveal a 33% reduction vs the 51% initial results.

Time will tell the overall picture but the longer one goes, the more chance the immune system will do the rest.

[Hopeful]

Becky,

I am not a numbers person, and I am hoping you can help me out here. Is the current article saying the original 50% rates diminish over time, such that the effect of the tx delays rather than prevents recurrence, or are the rates lower year to year because fewer people in both the control arm and the Herceptin arm of the trial recur each year as time from tx increases?

Thanks,

Hopeful

[Paris]

The 25% number jumped out at me too. I am assuming the 25% is in addition to the benefit derived from doing chemo which is 33%.

What I am extrapolating from this is that over time more people recurred bringing down the DFS percentage. I hope I am wrong!

[Christine MH-UK]

I was thinking that perhaps I need to point out some of the positive developments:

* The reduction in recurrence is still 25%, which we probably would have been thrilled with if the earlier reduction hadn't been so amazing.
* The statistical significance is still holding up for herceptin as a reducer of recurrence no matter how stringent the level is.
* 79% still have not recurred.

Finher has done well, too, but I'll put that news where it belongs.

[Debbie L.]

Okay, let's see if we can figure this out. First of all, the stats being reported are relative numbers, and as Paris said, are the difference between Herceptin/no Herceptin. Everyone in these groups got chemo, so chemo's benefit is separate.

Relative (vs absolute) risk reduction means you take your risk of recurrence before adding "brand x" (in this case Herceptin is brand x), and you apply the relative risk reduction (that brand x offers) to those numbers. So if you had a 10% risk of recurrence with surgery and chemo as your treatment, Herceptin brought that down to, uh, about a 6% risk of recurrence (10% minus 36/10 = 6.4). Or if you were high risk - say facing a 60% risk of recurrence with surgery and chemo - then Herceptin brought your numbers down to (harder math, hold on ... ) 38%. Please check my math. I'm clear on the concepts but muddy with the figures.

The abstract below (or above, depending upon how your page is set up) that started the thread said that the first HERA reports with two years of follow up (in 2005) gave 36/34% improvement for recurrence/death. So for whatever reason, that's the best HERA ever reported - no 50% improvement there.

Then this latest data at 4 years is showing a 25% reduction in recurrence but it's in the ITT group (intent-to-treat). So what I think that means is that even the "more than 50%" of women in the control group who elected to switch to receive Herceptin 2 years ago are included in the no-Herceptin group for statistical purposes. I'm not absolutely positive about this - is this crystal clear to anyone else? If that's the case, then these stats are at least as good as the original report and maybe better. What we don't have is more details about how that cross-over group is doing, which will be very interesting. But I'm pretty sure that it's their doing better that is bringing down the number to 25%. Also I wonder if they'll be able to compare only those who got Herceptin and those who didn't (leaving out the cross-overs altogether) and what those numbers will be. It's hard to be patient.

Debbie Laxague, going out for some fresh air to clear the brain-mud, but gathering lots of tire-mud on the bike.

[RobinP]

I am sure a lot of women who took Herceptin are reassured with this data, as well as Genetech. Interestingly, the trails were not designed for her2+ small cancers.

[Becky]

I went to ASCO 2006 with the group. They clearly are calling the crossover group the "Observational" group and are watching the results of 3 groups - herceptin, no herceptin and the "observational" group which is the crossover group.

Even the statements from the doctors in the article refer to the crossover group as different stating sometime like "even those receiving Herceptin late via crossover are seeing the benefits".

I asked a question during this presentation on how late was late (did the women who joined the study in 2000 but did not get Herceptin be allowed to get it). I wanted to know this because at the time, many women (even on this board) were eager to get Herceptin but were beyond the trial criteria to get it after the fact. The study doctors would not answer my question (they knew what I was asking too).

[RobinP]

Yep, Becky, I read you loud and clear, even late Herceptin has an impact. How much, is not clear, but it really only makes common sense that it would. I don't know anyone that got Herceptin as late as me, three years out, but I suppose it may have done something for me.
PS. Have you heard anything, Becky, about the subtypes of her2+ that was recently identified by Dr. Piccart in the 70 gene signature? Apparently, at all her2+ are the same and some are more aggressive than others and have more potential to relapse. I really haven't had time to look into this more, but am interested.

[Christine MH-UK]

Hi Robin,

I suspect that they didn't include small cancers because in many HERA countries such cancers were not believed to be high-risk enough to warrant chemotherapy, although more recent research suggests that that there is no such things as a truly low-risk her2-positive breast cancer.

[RobinP]

I follow the SABC and the ASCO breast cancer conferences and abstracts very closely and recent research has NOT clarified the risk of a small her2+ invasive bc 5mm or less. No retrospective studies or prospective studies have addressed the significance of the tiniest her2+ invasive bc relapse risk that have statistical power. You can't lump t1a and t1b tumors together and determine relapse risk for the t1a. Evidence based medicine is based on clinical trial data, not conjecture. There is much controversy even today in medicine as to the protocal for earliest her2+ bc treatment, t1a tumors because of lack of statistically significant data. I just had someone on these boards recently inform me that their mother had a small her2+ invasive bc of less than 5mm and the oncologists were not in agreement with herceptin treatment. There is a point when blood vessels have not yet formed on tumors where there is no ability to metastasize and spread, at exactly what point that is the golden question that needs clarification. Once the trails for target her2 systemic detection give us more clues, we may have that answer.