Need advice after progression on herceptin/avastin/navelbine

[erica35]

If any of you have the patience or time I could really use some real world advice to give to my friend (postmenopausal ER+ HER2+ stage 4) with liver mets. She's being offered a tykerb/herceptin bridge until she can get into a TDM2 trial. I've been reading up and have a few questions...

-For those of you who have used it how tolerable is tykerb?
-If she is already resistant to herceptin is the tykerb/herceptin bridge really going to do much for her? My thought is that it might a little but I'm not sure that this is what should be chosen after the first progression. I'm thinking that she might get better sensitization by combining tykerb with an anti-hormonal and then can go back to using herceptin again. Any thoughts or experiences about timing of new therapies after progressing on herceptin.
-I feel that now would be the time to try the T cell either the CEA or HER2 studies. Has anyone done them and what do you think?
-Do you know a breast cancer center specializing in HER2 metastatic cancer who you can recommend for second opinions?
-Those of you who did the TDM1 trial what was your experience?
-And finally but most importantly any advice on how best to support her emotionally through the first progression (8 months after mets diagnosis)? I feel like I don't know how to hit the right note between anger/hope/grief.

Thanks. I know how stressed many of you are and please don't feel obligated to respond.

Hugs, Erica

[Rich66]

You might want to list all prior treatments she's had to help people get ideas. If you look in articles of interest, I did post there about fulvestrant + chemo synergy. Perhaps it would make sense to add that to what she was just on. Might depend on the severity of the progression. i.e. would it benefit by a little something extra or is it totally failing. I think it might be wise to ask the onc about their view on cancer stem cells. Herceptin and Tykerb are both purported to kill CSC so the doc may be onto something.
Regarding TDM1 trial, I believe there were folks saying that certain characteristics were predictive of response. Might look into that issue while in holding pattern.

[Carolyns]

Hi Erica,

Read the post "Recent Update" Irene from Tampa about TDM1. She is having amazing results.

[chrisy]

Hi Erica,
Well, you certainly tossed a wide range of questions out there! Good for you to get them in writing, most people have it all spinning around in their heads and never can get it out!

First, your friend is very very fortunate to have you. You so obviously care deeply for her. Being there for her, and letting her know you care are the best things you can do. As far as hitting the "right note", you sort of have to take your cue from her. And it is a delicate balancing act for sure. But it's totally natural to bounce around between all those emotions like a pinball.

The first progression is hard, because you do lose the dream that maybe, just maybe it won't ever come back. It was hard for me to give up that dream, but I do find much hope that better answers are just around the corner.

You sound like you already have a great awareness of the kinds of work that's being done out there - the past week with all the reports out of ASCO has been really energizing. So you know that there are lots of (too many??) options out there that could work very well, and for a long time. The "good news" if you can call it that, is being ER+ and Her2+ means she's got a target rich environment, with lots of weapons to bring to bear.

I think I'll post separately on some of your other questions, but since I always lead with my heart, I just want you to know that whatever she feels, and whatever you feel, is OK.

[chrisy]

Hi, me again!

I've also been in a DM1 trial, since Feb 08 with great results. It is a very promising new approach and although it's a bit tougher than plain vanilla Herceptin, it's quite tolerable.

So, you see I do have some bias, but overall I think a TDM1 trial would be a very reasonable option for your friend. I think what you are saying in your post is that the Tykerb/Herceptin would be a short term thing, until she can get into the DM1 trial, right? If this is the case, the goal of the Tykerb/Herceptin is to keep things stable.

She has a "window" in which she will be able to get this drug on trial. She may not have another opportunity until after it is approved, which at earliest would be about a year. There are, of course, other types of trials out there as you note. But asTDM1 is further along than some of them, it has more data and has already shown efficacy.

I'd say, have her discuss the options (and why they are being recommended) with her oncologist. Bring up other thoughts as well.

Tykerb and Herceptin both target Her2, (Tykerb also targets Her1) but they do so in different ways. So Tykerb can work after Herceptin fails, and also there is some data that using the 2 in combination works well.

Tykerb is pretty easy to take, the main side effects are diarreah (which most people are able to manage with diet and Immodium) and in some cases rash. I found it very tolerable.

OK, next! "metastatic Her2 specialists"...
You didn't say where you/your friend are located, that might help people make suggestions. It's safe to say that any Comprehensive Cancer Center doing research treats a lot of metastatic disease, and also that much of the research going on is on Her2 targeted agents. Still, there are some who are specifically on the leading edge of this research.

I know I didn't answer your question. I was referred to a top research oncologist by...my local oncologist. The good ones are both familiar with and eager to work with the top docs. So it doesn't hurt to ask for a referral.

Chris

[chrisy]

Ha Ha - you probably think now that I have a ton of time on my hands! But really, I just don't want to go make sloppy joes.

Thought I'd share a little more detail on my experience in the TDM1 trial.

Sometimes choices really are windows opening when a door has been closed.

I had progression after 8 months on a Tykerb/Avastin trial. Needless to say I was bummed. So I'm sitting there with my rockstar oncologist and ask her "well, what now"?

She starts rattling off combo after combo after combo...before saying "or there's yet ANOTHER trial". It was the TDM1 trial that I had been reading about but was not open at UCSF. Yet. But it was in the process of opening there JUST as I needed it. Coincidence? I think not - that's what I mean about windows and doors...

Anyway, I had my first treatment on Feb 11 2008. In that trial, the first infusion is pretty much an all day affair. They infuse over 90 minutes, monitor your vitals and take blood samples over the course of the treatment and for 4 hours afterward!

Side effects are mainly like herceptin only a bit more intense. After my first infusion I got a fever and mild flu like headache, still get that but milder and easily controlled with an advil. Most people have a drop in platelets (which rebound quickly) and many people have elevated liver enzymes.

I had a really wacky side effect, 2 days after my first infusion I had extreme pain in my liver (I, too, had liver mets). So much so I could barely breathe. This lasted a few hours and that was that.

I chose to believe that pain was screaming cancer cells dying. I don't know if that's what it was, but my first scans after 6 weeks showed the major areas of interest reduced by half in size and metabolic activity. And the minor areas that had begun to "light up" were gone. After a few months, they could not see any evidence of metatstatic disease.

My main side effect has been elevated liver enzymes - this made me have to go to a 4 week instead of 3 week schedule. I found a liver cleansing diet with the main elements being beet juice and carrot salad which has worked well and keeps me in the "treatable" range.

I met the lead doctor on the study at the San Antonio Breast Cancer Symposium last December. She told me I should have stood up in the crowd when she was reporting the results and shouted "hey, that's ME"...but I'm just as happy being a quiet beneficiary of this exciting new theraputic approach!

Ok, I PROMISE I will shut up now!!!! I just felt that since I had personal experience with several of your questions, I had to pipe in.

Take care, let us know how it is going with your friend.
Chris

[erica35]

Thank you all for your suggestions. She is currently on tykerb/herceptin while awaiting TDM2 trial. I hope she gets some stability and I hope she gets into the TDM2 trial. Thanks for the advice. Erica