could someone explain the Herceptin/DM1

[micheleu]

i've been off the website for awhile and i don't understand this new Herceptin.

[chrisy]

Herceptin DM1 is a first in class drug which links a toxin (DM1) to a herceptin antibody. The Herceptin targets the her2 protein as regular herceptin, then once it docks with the her2 receptor, the DM1 is released within the cancer cell and kills the cancer cell. So, instead of relying on the herceptin to stop the cancer, you are using it as a targeting mechanism to deliver the toxin (which kills the cell). Is has been likened to a "smart bomb".

At San Antonio I saw the poster presentation, and one of the comments was that they had never been able to use the DM1 in therapy because it was "too toxic"...so they were excited about the herceptin DM1 because they could now deliver it directly to the cancer cell with minimal toxicity to normal cells.

The full name of the drug is Trastuzumab-MCC-Dm1 with the MCC being the "linker" molecule. This is critical as in earlier efforts to do this, the linker would not "hold on" to the toxin long enough, but the MCC does.

Not a super technical explanation, but it is fairly accurate!

They are now beginning adjuvant trials to see if the T-DM1 could be given instead of chemo + herceptin, with good efficacy but far less toxicity and side effects.

[Sherryg683]

Some other questions...is this given only with active cancer. Is it for stage IV only or can it be used at any stage. I am currently on herceptin indefinately but have been NED for awhile, is this something I could take instead of my normal herceptin? I'm going to do a little research but I never seem to understand that technical stuff they write..sherryg683

[runtolive]

sherry. i believe the new trials about to begin will be in MBC metastatic breast cancer patients who have failed other regimens. one trial will be a phase 2 trial for patients with measurable disease who have failed tykerb. this will be a 3rd line setting trial. and could be registrational and thus approvable if and when the data shows superior efficacy to the tykerb. which should not be too difficult imo.

the other phase 2 trial is in a first line setting and is very exciting.

tras-dm1 vs herceptin + taxotere. to measure PFS

i have seen numbers for the H + T pfs around 6-7 months.. not very good. where as tras-dm1 has shown PFS around 9.6 months in early phase 1/2 trial data. approx 125 pts..

genentech is also comtemplating a pivotal phase 3 trial in a second line setting but i dont know any of the particulars yet.

sherry .. since you are NED. you would not be eligible for tdm1 . hopefully you wont ever need it.

run to live

[Sherryg683]

What is PFS? ..sherryg683

[SoCalGal]

progression free survival - I think.

[runtolive]

sherry.. PFS is progression free survival.

tras-dm1 is a fabulous drug. and the sooner its gets approved the better ...imo it will become first line treatment, before chemo for all her 2+++ breast cancers .. within 5 years...

[grandma2]

wondering if they would use it if the original herceptin failed or would it still be something they might try for IV patients.

[chrisy]

You're right, Runtolive, the upcoming trial for T-DM1 vs herceptin + chemo is for first line metastatic disease, not adjuvant therapy.

There is so much discussion about this drug, sometimes I forget what is ACTUALLY on the horizon vs. what is speculation about the future...which I think, should this therapy prove as effective as we hope, would be finding those who can get adjuvant benefit from this approach instead of chemo.

[Sheila]

I am hoping I can qualify for this since it is coming soon....I may need to stay on the Taxol a while longer rather than switch...I find out next week what the criteria is. I am excited it is coming where i go for treatment...only one other place has it in Illinois right now, about 145 miles from me. Chrisy is it weekly?

[chrisy]

Sheila,
I don't know for sure which trial you are trying to get into - I know one of them looks like it requires having had lapatinib so maybe you would get to be a diva for a bit first...but you should get your trial coordinators working on THIS knowledge now so you will be ready when the trial is ready. Check out any "washout" requirements and scan schedules as well.

The trial I'm on is IV infusion every 3 (or in my case, 4) weeks BUT requires weekly labs and office visits! In the trial I'm on these cannot be done locally I have to go up to SF. I'm not sure which is worse - having weekly treatment or having to drive 150 miles for a 15 minute exam!

Of course, I'm happy to do it if the treatment works - as I know you would be. But we do need to have something to gripe about, don't we! The positive side is, there's no premeds (I know you'd miss that) so you could make a shopping and pizza day of it.

I'm hoping this trial would work out for you, I know you need a break from the taxol train!

[micheleu]

Ok i'm trying to understand this...is this what they've been wanting to do with the gold particles in nanotechnology? I went to a conference on nanotech. and they said how they wanted to attached a "smart bomb" chemo like particle to gold so small it would seep into the cell and kill the cell from within. It sounds like instead of using a gold particle they are using Herceptin because it targets the cancer. If this is so, that is awesome they are already doing this with herceptin!!

[runtolive]

micheleu.. it costs more than gold .. but no.. its not gold treatment...

its actually herceptin with a toxin (dm1) attached to it.
the herceptin acts as a carrier mechanism to deliver the dm1 toxin directly to the cancer cells, then the herceptin penetrates the cancer along with the toxin. then hopefully kills the cancer.

genentech just released data last week at the breast ASCO in DC., covering the 1st 30 patients treated with tras-dm1 in a phase 2 setting.

the data revealed 1 CR complete response after 10 doses of this drug, and 12 PR , partial responses, and 10 ladies had stable disease. so depending on how u like to call your data..
23 of 30 women are benefiting from tras-dm1..

or 13 of 30 had significant response..

genentech, makers of this drug, are also evaluating whether or not at announce a pivotal phase 3 trial as a second line setting. this announcement is expected before year end, but could come at their october conference call.

they are about to start 2 phase trials .... in 1st and 3rd line settings in MBC. orginally expected to begin in july 2008 but now looking like oct 2008.

run

[Rich66]

Seems so primitive and exclusionary to have to travel so much. Should be able to use standardized labs and video conferencing/imaging.

[hutchibk]

Chrisy - this is a question base solely out of curiosity, but do you lose your hair on this treatment?

Rich - I wonder if it is primitive and exclusionary or is it necessary control to get the most accurate results?

[Rich66]

It's probably the latter..just frustrated.

[chrisy]

Brenda - no, this is not a hair challenging therapy.

Rich - not sure exactly what you're talking about; I know for the trial I'm in I HAVE TO get all my tests etc. at UCSF which for me is 150mi RT. The reason they explained to me was so that they could be SURE they had standardized labs, tests, etc. I guess I understand this - they need to make sure the data is valid - but I agree, it would be nice if it's easier. As far as getting the drug, that does have to be there because it is not really available, so they get just what they need from Genentech.