Tykerb/Herceptin

[Esther]

I started taking Tykerb as soon as it was approved in March 2007, things were going really well, until my onc thought I should drop the herceptin and stay on just tykerb. Why I don't know.....I went with and within about 50 days saw some progression in what was thought to be scar tissue in my liver.

Went back on Herceptin, and also had cyberknife done in March 08, on the one liver met. The rads onc. at Stanford, indicated that the first, largest lesion is often difficult for chemo to get.


Shortly after that, I secretly went back on tykerb as well as the herceptin i was getting at my dr's office. I still had a supply on hand and started with that. I was thinking in terms of prevention, since i have already been diagnosed with brain mets.

I'll have an MRI and appt with the neuro at Cedar-Sinai next week, so we'll see if the Tykerb is helping any.

Last week my onc told me to add the tykerb to the herceptin, I just said, "hm...ok, I may need a refill called in...."

So know I'm on just tykerb and herceptin and hoping for the best.

How many women are on just tykerb and herceptin and having good results?

[hutchibk]

Hi Esther - I am still just on Tykerb/Xeloda and doing well, but we are monitoring closely and if anything new shows up in body or organs, we are going to add Herceptin straight away. I think Chrisy is on Tykerb/Herceptin and maybe even Flori...

Do you tolerate it well? So good to hear from you!

Brenda

[Lani]

I was told the article is to come out soon in ONCOGENE


Home > Abstracts & Virtual Meeting > Abstracts > 2008 ASCO Annual Meeting

Effect of lapatinib on accumulation of inactive HER2 at the cell membrane and on antibody-dependent cellular cytotoxicity (ADCC) mediated by trastuzumab: A novel mechanism for the enhanced effects of combined anti-HER2 therapy.
Sub-category:
Tyrosine Kinase Inhibitors
Category:
Developmental Therapeutics: Molecular Therapeutics
Meeting:
2008 ASCO Annual Meeting

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Abstract No:
3594
Citation:
J Clin Oncol 26: 2008 (May 20 suppl; abstr 3594)
Author(s):
M. Scaltriti, C. Verma, M. Guzman, J. Jimenez, J. Parra, K. Pedersen, S. Landolfi, S. Ramon y Cajal, J. Arribas, J. Baselga
Abstract:
Background: Lapatinib is a HER2 tyrosine kinase inhibitor that has clinical activity in HER2 overexpressing (HER2+) breast cancer. In vitro and clinical studies have shown that lapatinib enhances the effects of the monoclonal antibody trastuzumab suggesting partially non-overlapping mechanisms of action. In order to dissect the differential mechanims of these agents, we have studied the effects of lapatinib and trastuzumab on receptor expression and signaling and have explored a new potential mechanism underlying the profound antitumor activity of the combination. Methods: HER2+ breast cancer cells SKBR3 and MCF7-HER2 were treated with lapatinib, trastuzumab or both. Assays of receptor expression, phosphorylation, signalling and tumor growth were performed. Trastuzumab-dependent cellular cytotoxicity was measured with different levels of HER2 expression and doses of lapatinib. Results: Lapatinib treatment of HER2+ breast cancer cells inhibited HER2 phosphorylation, prevented ubiquitination and resulted in a marked accumulation of inactive receptors at the cell surface. By contrast, trastuzumab caused enhanced HER2 phosphorylation, ubiquitination and degradation of the receptor. By immunoprecipitation and computational protein modelling techniques we further demonstrated that the lapatinib-induced accumulation of HER2 lead to stabilization of inactive HER2 homo- and hetero-dimers. Accumulation of HER2 induced by lapatinib and downregulation of HER2 mediated by trastuzumab were also observed in vivo, where the combination of the two agents triggered complete tumor remission in all cases after 10 days of treatment. Lapatinib-induced accumulation of HER2 at the cell surface markedly enhanced trastuzumab-mediated ADCC. Conclusions: Lapatinib results in a marked accumulation of inactive HER2 receptors at the cell surface both in vitro and in vivo. This increase in receptors number at the cell surface enhances ADCC by trastuzumab. We propose that this is a novel mechanism that may be clinically relevant and exploitable in the therapy of patients with HER2+ tumors

Best of luck and Let us know how you do!

[chrisy]

Esther, I just love the way you take charge of your treatments - I mean, secretely adding Lapatanib back - Wow!

For the record, Flori is on Herceptin/Tykerb.

I'm not, I am currently on Herceptin-DM1 trial.

Hope you get good results from your "authorized" combination!

[Kim in DC]

Esther,

Secretly adding Tykerb sounds like something I would have done. I am glad you started this thread because I was thinking about asking my onc today to add Herceptin back. Now I have some ammunition. I had a complete response to T/X and I am trying to hold on until some of these super Herceptins get approved.

Kim

[Esther]

I know it was a bit sneaky to go back on the Tykerb on my own, but my gut was telling me to do it. I had been on both Tykerb and herceptin initially in April 07, and had no problems, so I figured it would probably be ok

If I did not have brain mets, I probably wouldn't have gone ahead and done it. I have follow-up MRI and Neuro appt at Cedars-Sinai next week, so we'll see if it is maybe helping a bit.

I'm big on following my intuition. I've always been right so far.

[Faith in Him]

I agree with you. When I first learned of my local recurrence my dr wanted to take me off herceptin. My gut was telling me to stay on it. I fought him on it and he finally agreed. When I got a second opinion at UCSF, the onc. there felt I needed to stay on herceptin too.

[Adriana Mangus]

Hi Chrissy:

Hope you are doing well.

How did you get on this trial? Did you get input from your onc.? I'm gathering as much info as possible before I see my doc in October, just in case the scan shows progression to the lung.

I have only been on Navelbine; twice+ Herceptin, so I have a long way to go. That's my hope.

My onc has been great and sent me for radiation which I completed in March'08. So far, I feel good. But you know how this works, aprehension sets in and you think the worse, real or not.

Big Hug and so much Love to you.

[Adriana Mangus]

Oncogene? Anyone knows the website, please. Thank you.

[runtolive]

adriana

here is a link to the old tras-dm1 study. click on the 40 site locations.. for one near you.. ucsf should be reopening with the newer trials shortly.. or call michele fernandez at genentech..

ucsf is not listed but we know they treat patients there..

http://www.clinicaltrials.gov/ct2/sh...ow_locs=Y#locn

run to live

[chrisy]

I was already on a trial at UCSF (tykerb + avastin) and progressed while on that trial...just as they were about to open the Trastuzumab-MCC-DM1 trial there. So for me it was a case of being in the right place at the right time. I will say that what has helped me most is I had a "regular" follow up with my 2nd opinion guru (Dr. Rugo at UCSF) so when I needed it, I had pretty good access. That was how I came to be under her care for the tykerb/avastin trial and now the DM1 trial.

If I remember, you are in Southern California, right? I know that other DM1 trials are getting ready to open, but I don't know where.
There is also some talk about trying to reopen the one I'm in (but I don't know what the status is on that, or if it's just a rumor).

If you have a good onc in your area, ask about the trials or as runtolive suggests, contact Genentech. Do not rely on the "list of locations" because it is NOT accurate - the trial I'm in has never updated the original 40 sites even after new sites were opened.

There is a lot of interest in this new drug - so there is a good chance there may be a study near you if you should need to make a change.

And by the way, DELIGHTED to see you are "still kicking"!

[SoCalGal]

Hi Esther-

I'm on Tykerb-herceptin and avastin. Dr Glasby at UCLA told me not to stop tykerb when I had progression on tykerb xeloda but to add in herceptin. He used the analogy of a road block - if some "cars" are getting by add to the road block don't remove it entirely. I'm hoping that sometime soon I can stop the avastin and just stay on herceptin-tykerb. (Or I would take a cure - either one).
xo Flori

[Believe51]

Trying to get my ammo ready because I do think we are going to try this combo next. We gamma-knifed 10 spots that are dying right now. We just found another brain met, tumor markers rising again.....think we have bone progression. Will know more after further testing.

What are your opinions for adding a chemotherapy element to this combo?? Flori, your opinion will be appreciated if you have a moment, as well as all responders. Thanks>>Believe51

[hutchibk]

Esther and Flori - also, how many Tykerb are you on? I am dropping to 4 instead of 5, because the combo of it with Herceptin in causing gastric/bowel distress for me.

[SoCalGal]

Just a quick response - I am on 5 tykerb a day. I had a lot of trouble at first but when I stayed on 3 pills for four days and then 4 pills for four days I was able to get up to 5 pills without problems. I still have the runs but not all day long and my tummy is not growling and swirling all day long. BUT I can no longer eat lettuce (salads) as I don't digest the leaves. There are weird things like that. Or I should say if I eat salad I will have the runs (somewhat) later. While I keep a bathroom in mind I no longer have to keep one in site. It took me several months to adjust this well. Adding in the herceptin kicked it all up a notch but now it's routine and doesn't control my life. At all. When I travel I drop down to 3 pills that day and have no side effects. My biggest s/effect is fatigue an hour after taking the tykerb. I feel pretty good energy in the morning but then the tykerb slump sets in. I guess that wasn't very short.

Marie - what about the DMC trial? The one that Chrisy's on?

Getting my triple drip today. Will post later. Have much to update...

[Julie2]

I am on Herceptin and Tykerb (5 pills a day). So far I didn't have any side effects except the dry skin and chopped finger tips. Hope this helps.

Julie

[hutchibk]

Thanks, Flori - very helpful.

[Adriana Mangus]

Hi everyone:

I have been on Herceptin since 2003, every three weeks, 30 min infusion.

On October 17 I started taking Tykerb, all was good until wednesday when I developed itching behind my ears, redness, and both of my ears felt really warm. Wednesday night I developed little pimples on legs and arms. I read the phamplet (insert) that accompanies the prescription and it says to stop the medication immediately if any of these symptoms present while taking Tykerb.

Anyone of you had this reaction? Just my luck? I'm depressed I was happy to have Tykerb on my side but with these symptoms I can't continue taking it.

Should I call my doctor or wait until I see him December 5th.

The worst thing is that I have the feeling that it is working; it kills me to have to stop it.

Anyone, please, could you respond. Any ideas will be appreciated.

[Julie2]

Adriana,

I do have small pimples around my nose and forehead because of Tykerb. Also dry skin. My onc. seems to be not concernced.

Julie

[jones7676]

I know I tried to keep taking the two and my doctor was not cooperative and so I'm back on Herceptin. I want to be on them all!!!!!!