Herceptin/T-DM1 trial ?

Faith in Him · 09-29-2009, 07:50 PM

If you did not respond well to herceptin, would it be reasonable to assume that you won't respond to T-DM1?

schoonder · 09-30-2009, 07:14 AM

Administration of t-dm1 in many instances rejuvenates the herceptin activity.
Current her2+ mbc t-dm1 trials are showing that agent is efficacious where originally herceptin didn't work at all or failed to be beneficial after a given period.
Pre-clinical tests proved that herceptin stand-alone continued to work again after stopping t-dm1 dosing.

Faith in Him · 09-30-2009, 09:44 PM

Wow. That's interesting. Thanks for the info.

chrisy · 10-01-2009, 11:28 AM

I asked that question before starting this trial: If Herceptin stopped working, why would DM1 work now?

The response I got was because it's different. With DM1 you are not relying on the herceptin to stop/kill the cancer, the herceptin in simply a delivery mechanism for the DM1. So you deliver the DM1 - which is a very powerful toxin - and that is what attacks the cancer.

In my case, I had a good response to herceptin but after a time this alone was not enough to hold the cancer at bay. But it has worked very well for me in the DM1 trial.

Schoonder, I was particularly interested in your comment "Pre-clinical tests proved that herceptin stand-alone continued to work again after stopping t-dm1 dosing." I hope this is true!

My secret plan is to have the dm1 continue to work, then eventually keep that in the mix with alternate/combined therapy of tykerb and plain herceptin...

schoonder · 10-01-2009, 02:22 PM

If sufficient herceptin resistant cancers cells are killed off during the t-dm1 cycle, then "naked" trastuzumab could become efficacious again.
Don't believe that this ability has been evaluated in clinic.

chrisy · 10-01-2009, 03:43 PM

Schoonder - yes, that was my thinking as well. Pretty sure you're right on it not having been tested clinically yet, as they are still running the initial Phase II trials to see if it even works!

Carolyns · 10-04-2009, 09:55 AM

I have been on and off Herceptin for almost 4 years now. It has never worked for me alone although once I got 3 months out of Herceptin / Tykerb (no chemo).

I have just completed my 4th week of TDM1 had my second dose a week ago last Friday. On Thursday I began to notice the two lumps on my chest shrinking and flattening. This has always been a good indicator for me so maybe it is working.

It seems like the most important factor to entry to the trials is confirmation of Her2 status and not prior failure on Herceptin and that says a lot to me.

Best wishes, Carolyn

schoonder · 10-05-2009, 06:32 AM

Carolyn, with effort you've put out to get into this trial at Karmanos, I'm thrilled you're seeing excellent early activity from the combined T-DM1 and Pertuzumab administration.

Carolyns · 10-05-2009, 08:32 AM

Hi schoonder,

Thank you for your kind words. I am currently getting the TDM1 alone. The Pertuzimab would be added if I progress.

Thanks, Carolyn

Kathy T · 10-10-2009, 05:44 PM

Carolyn,
I think I am on the same trial as you are-- I receive Pertuzimab if i progress--I have received to txs. of TDM1.
Kathy T

Carolyns · 10-17-2009, 10:38 AM

Faith in Him - How are you doing? Are you considering TDM1? I hope that you are doing well.

Kathy, I just finished my 3rd treatment. It is getting much better for me... the first treatment was hard and 2nd easier and 3rd better yet. Scans in 2 weeks. I hope that you are doing well.

Carolyn

Kathy T · 10-17-2009, 10:51 AM

Thanks Carolyn,
I will have my 3rd tx. in another week-followed by scans 2 weeks later--I am hopeful too.
Kathy t

Rich66 · 11-03-2009, 04:22 PM

Any thoughts on borderline levels of Her2 and T-DM1? My mom's primary years ago was technically Her2+ but her recurrence liver biopsy was borderline Her2 negative and strongly ER+. She has had Herceptin with Navelbine based on initially elevated serum her2 but that combo is failing her.

Carolyns · 11-03-2009, 04:36 PM

Hi Rich,

I am sorry to hear about your mom. As far as Her2 status. The sample of mine that the drug company insisted on using was very specific. In my case it was a sample that had been Her2++ which would have excluded me from the trial. When their labs retested it the sample was Her2+++ and I was accepted. I hope that I have me pluses right. Anyway, they cut the sample into many slices as I understand it and the Her2 status worked. Otherwise they would not have accepted me into this trial.

I have you and your Mom and family in my prayers.

Carolyn

Rich66 · 11-03-2009, 04:49 PM

Are you referring to metastasis or primary biopsy?
This issue of limited/variable biopsy sites really has ramifications. It pains me to think that the random selection of biopsy site might disqualify someone from effective treatment. I know there is suggestion that breast cancer stem cells are Her2+ and ER-, regardless of biopsy.

Carolyns · 11-03-2009, 06:29 PM

Hi Rich,

I am not sure about this. All I know is that the trial seemed quite specific about the tumor sample that they wanted and it had to be of ample size to get a bunch of "slides" out of it for the drug company to run it's own tests. This was my perception. It could be that it was the only sample that they could get but the messages were mixed on that. It was a very tense time for me. I have read many times that the Her2 testing as well as hormonal status can be quite flawed and results differ based on many variables ... so I guess that the drug company needed to make certain that the participants had the amplification needed to give the drugs the best shot at response.

The biopsy was from the mets but there could have been other samples sent and tested.

I hope you find the right thing for your Mom soon.

Sincerely, Carolyn