Apples and Oranges

[Joe]

Both Lisa and Paul are correct, which is why only your onc should interpret the results of breast cancer studies.

I am familiar with the MD Anderson report that came out the first week of June. I am also familiar with long term statistics about HER2, Herceptin, and remission.

First of all Lisa is correct. Statistics confirm that only 25-30% of HER2 positive bc patients have long term success with Herceptin. This percentage is measured using the standard 5 year survival rate. In fact Genentech is now doing studies where they follow HER2 bc patients from their first diagnostics to their eventual remission or recurrence. These studies started late in 2003 and results probably won't be available for a few more years.

BUT and it is a big BUT, Many chemo treatments show initial success but then the patient grows "immune" to the drug and the success is short lived. This includes Herceptin, which is why onc try Herceptin in combo with other chemos, sometimes after only a few treatments.

I believe the interpretation of the results of the MD Anderson studies are clouded due to this phenenoma. The MD Anderson studies were designed only to study pre-operative treatment of tumors with Herceptin and then only for a short period of time. It aims did not include long term survival. Also the MD Anderson studies did not use Herceptin as the sole therapy, but added other drugs to the cocktail.

Warmest Regards,
Joe

[Paul]

Dear Joe,

Let me provide you with some additional context. Lisa indicated in her post that the effectiveness of herceptin in the case of a recurrence is 25% to 33%. Initial treatment with herceptin plus other chemo drugs such as navelbine or taxotere (with a platinum salt) has reached effectiveness rates in excess of 60% percent (including the most recent UCLA herceptin+taxotere+carboplatin study). Lisa was not clear as to what type of "effectiveness" she was referring to in her post. On this basis, the stat is wrong. If Lisa, as you suggest, was actually referring to intermediate or long-term survival data (e.g., 50 to 60 months) with respect to HER-2 positive breast cancer patients, I would submit that reliance upon the Vogel, Slamon et al. survival data (created in 2001 or earlier) is dated, and arguably obsolete, in light of today's technology in the event of recurrence. For example, the old studies and graphs at www.her2status.com (which set forth such percentages) relate to studies published in 2001 and earlier. At that time, it is my understanding that chemo drugs like navelbine and taxotere were not factored into the study. Nor were more recent drugs like lapatinib or iressa or xeloda or gemzar or APC8024 factored into those studies. In sum, if you look to 25% or 33% as survival data for herceptin at five years today -- I submit that it is improper to rely upon studies three or more years old for survival data.

I'm also wondering how anyone issues effectiveness data on the use of herceptin when herceptin is almost always combined with one or more chemo drugs throughout Stage IV treatment. How are the various chemo drugs factored into the Herceptin effectiveness stat? Does the stat refer to node positive HER-2 women or node negative HER-2 positive women or a mix of women with respect to the stat?

Again, Lisa's post stated a 25% to 33% "effectiveness" with respect to herceptin in the context of recurrence. It was not clear what "effectiveness" she was referring to in the post, nor why she was referring to herceptin as a treatment in isolation. My understanding is that the relevant stats are initial treatment effectiveness, time to progression, and survival stats at, for example, 5 years and 10 years. If Lisa intended to post Herceptin survival stats, I would contend that the stats are incorrect based on today's technolgy. The 25% to 33% survival stats are clearly dated (generally 2001 or earlier)and quite frankly, are misleading in my opinion.

Lisa is fond of posting the comment that we should consult with our doctor first and not rely upon board statements alone. This is one instance where I think it was proper to follow her advice and not post what appears to be intermediate survival data. I hope this clarifies my position.

In any event, I would appreciate if you would post on the website the Genetech or other statistics you are referring to in your post so we can better understand the context of those "herceptin effectiveness" stats.

I find your observations regarding the M.D. Anderson study confusing. Of course the study was designed to address the neoadjuvant context. That is the context in which all newly diagnosed women want to beat the disease. The study did not address a significant time frame because it was discontinued for ethical reasons due to the amazing results so as to allow the control group women to switch treatments. As you know, a discontinuance "ethics" clause is common in clinical studies when the group conducting the study feels the control group would lose out on beneficial treatment if the new treatment was denied. As you know, a similar step was taken in at least one other anti-estrogen treatment study. The statistical analysis set forth in the M.D. Anderson study showed expected beneficial treatment for all 167 patients at 98% certainty assuming the study had continued. You also need to explain why M.D. Anderson, a top ten U.S. cancer center as ranked by U.S. News and World Report, made such treatment the standard of care for newly diagnosed, early stage HER-2 positive breast cancer cases. The study results are not clouded because Herceptin was combined with other chemo drugs. Herceptin has been found most effective when it is combined with various chemo drugs in several contexts. Herceptin has only been used as a monotherapy for recurrences in studies conducted by Drs. Slamon and Vogel in the past. It is generally used as monotherapy today once a patient reaches NED.

I look forward to your post setting forth the "herceptin effectiveness" statistics.

Warmest regards,

Paul