I don't have a lot of time, but I wanted to share some impressions about the ASCO session today at which data on three major adjuvant Herceptin trials were reported for the first time in detail. Tomorrow you will be able listen to the details yourself on the Virtual Meeting at the ASCO website ( I will post it).

The NCI had already reported preliminary results from a joint analysis of both the NCCTG and NSABP trials on April 25. These data showed that women who received Herceptin after 4 cycles of Adriamycin/Cytoxan and with Taxol, had a 52 % decrease in risk for breast cancer recurrence and a 33 % decrease in risk of dying when compared with women who received the same chemotherapy alone. Okay, so you knew all of this already last week. Today, we also heard data presented from the large HERA study done internationally of 5090 women in 39 countries around the world. In this study, women were randomized to receive Herceptin every three weeks for a year, two years or observation, after any adjuvant chemo of their oncologist's choice. In this trial, a third of patients were
node-negative. In all the trials, about half of patients were ER/PgR+.

What I learned today was that the decrease in distant disease free survival (DDFS) which is strongly predictive of overall survival (OS) is even greater, at 53% That means that more than twice as many patients had metastatic disease without the Herceptin! When I saw those diverging curves, it sent chills down my spine. Then it brought tears to my eyes as I thought of all the young women with HER2+ breast cancer I've known who died
of this disease and how in the future that number will be cut in half, or more. That's a HUGE benefit, in adjuvant treatment, larger than any we've seen in the last 25 years. And the benefits of Herceptin apply all across the board, to all patient groups, regardless of age, number of nodes involved, and ER/PgR status. Moreover, among the Herceptin treated patients the chances of recurrence, which increase in the second year, start going down shortly thereafter and keep decreasing, so the chance of getting metastatic disease actually appears to be going down over time--so far. It is a short median follow-up of 2 years.

We talk about levels of significance in reporting clinical trial results, with the usual P values having to be less than 0.05 for the results not being due to chance. Well, the P value in this analysis was 2P=3x10-12. I have no idea how many zeroes this represents, but let's just say there's not a snowball's chance in hell this data can be explained any other way than as a benefit of Herceptin. The hazard ratio of DDFS is .47.

There is a very significant difference in deaths, even at 2 years. One very striking and sobering finding is that almost a third of HER2+ patients who didn't get the Herceptin had a recurrence in the short follow-up of the study.

Of course, these benefits do not come without costs--principally in terms of cardiotoxicity. While there were no deaths, there was significantly higher cardiotoxicity in Herceptin-treated patients, varying somewhat across the studies, higher when Herceptin was given concurrently with Taxol (but slightly greater efficacy). I didn't get all the figures, but it looked to me as if it falls in the neighborhood of 4% or so. This is not a small number, and is cause for concern.

This concern may be addressed very soon, when the efficacy results from the BCIRG 001 study are released. This study had three arms, Adriamycin/Cytoxan-> Taxol, A/C->Taxol/Herceptin, and Taxol, Carboplatin, Herceptin (TCH). So this study was the first to examine a non-anthracycline-containing regimen, and the cardiotoxicity data were presented at ASCO. Turns out there was only one case of heart problems in the TCH arm, and 18 in the AC->TH arm. So it seems as if it's the administration of these two drugs in close proximity that is causing the heart problems--which are, for the most part, reversible and treatable, by the way.

Finally, if the efficacy results for the BCIRG 006 TCH arm are as impressive as everyone seems to be hinting they will be--then HER2+ patients may not be getting anthracyclines like Adriamycin or Epirubicin as adjuvant treatment.

After these results had all been presented, this audience of some 10,000 people came as close to standing up and cheering as any I have ever seen at a scientific meeting. What a day!

Sorry if I've been too technical for many, but I wanted to share some of the excitment from down here. I'm sure you'll hear lots more in the media about all of this.

I'm too tired and happy to take on the thorny issues these findings raise--there is much to be done about improving testing procedures, and beginning to talk about how in the world we can afford to pay for a year's worth of Herceptin for a quarter of all breast cancer patients--all over the world.