Roll call, advice, TDM1?

SoCalGal · 05-22-2010, 11:52 PM

Hi all,
I know many are having success with TDM1. I am meeting with the clinical trial onc on Monday for the expanded access trial of TDM1. I will post whatever I learn, but am trying to think up questions. Feeling scared about change from Herceptin/Avastin/Zometa & Tykerb, although I have been off Tykerb for about 4 weeks now.

My markers are rolling up - my onc said I should go back on Tykerb. My onc said that I could stay with what I'm on (adding in Tykerb) OR try TDM1 - she did not say I was jumping the gun and said I could go back to this regime if Run DMC didn't work.

I have always thought that it will work for me but maybe wishful thinking. Not even sure if I will qualify - my scans MUST show progression. It's confusing because I am not a clear case - last PET/CT said, "stable, intensely metabolic..." in referring to my sternum mets. The word stable needs to go away. Intensely metabolic is not good and it's been like this for 3 years. Since my stage 4 dx, the sternum mets have not gone away, despite multiple treatments AND let's not forget the radiation.

Is it risky to try TDM1 without tykerb? What about the brain invaders? Will they try to reappear? Or if TDM1 gets rid of the body mets, will that prevent the invaders from roaming? I will have to travel about 2 hours for treatment, again, new stuff out of my comfort zone. Do-able but adds anxiety and stress.

I'd appreciate any words of advice or info on side effects. How tough is TDM1? What's the worst side effect? I've wanted this drug for so long...I just think it will NED me.
With gratitude, Miss Flori-dory

Barbara H. · 05-23-2010, 11:33 AM

I highly suggest that you go on T-DM1. It was a miracle drug for me. I entered a phase 1 trial in Sept. 97. I had enough pain in my hip that I could not sleep for more than two hours at night. Within two days after my infusion the pain was gone. Unfortunately, I developed lung inflammation as a side effect and went off the drug last October. However, I am the only known case with this side effect. I only felt as if I had the flu after the first long day of infusion. Nevertheless, I had to be in school that evening for Curriculum night to conduct a program for my parents in my classroom. The next day I was fine. The only other side effect that I had were frequent nose bleeds. My liver enzymes also increased. That is normal for this drug. I loved this trial because it was really no different than taking Herceptin and I felt fine. I was NED the entire time I was on this drug. However, I can really only say that I don't have measurable disease, because the bones will always show that they have been affected. That is also true for any trauma they have experienced.

In spite of my side effect I could use this drug again once it is approved. I just have to be continually checked for lung side effect. I am currently on Tykerb and that is also working for me.

Feel free to check my posts over the past 2 1/2 years.

Good luck,
Barbara H.

Kathy T · 05-23-2010, 05:15 PM

I have been on the T-DM1 trial since last Aug. It has stablized my bone mets, although they have not regressed. i have much less bone pain and a fx. acetabulum has at least partially healed. The side effects have been minimal for me--very slight nausea for 2 days--lowered platelets and elevated liver enzymes. The last 2 infusions resulted in allergic reactions--received Benadryl which helped. I wish i could stay on this combo forever--i feel so great. Good luck with your decision.
Kathy T

1rarebird · 05-23-2010, 05:37 PM

SoCal---Kathy and Barbara are so much more knowledgable about this than I am that I hesitate to add a comment. However, I have been reading quite a lot about the cross-talk phenonmon which occurs amoung the growth regulating recpetors (Her2 ane ER in particular). It has been recommended by more than one reseacher that blockading Her2 at both ends of the recepetor helps if not stops cross-talk and proliferation. Tykerb and Herceptin ( I believe TDM-1 too) should achieve this dual blockade. This is especially important with ER+ Her2+ cancers.

Good luck with you oncologist tomorrow.

bird

SoCalGal · 05-23-2010, 08:14 PM

Thanks for the good input...just finished organizing my duplicate GIANT file. Feel like an attorney going to argue my case.

schoolteacher · 05-24-2010, 07:10 AM

Thinking of you Flori. Hope you get in the trial.

Amelia

Lani · 05-24-2010, 08:54 AM

1 rarebird--
What crosstalk are you referring to?

I have seen no papers indicating that blocking the her2 receptor via BOTH its internal and external domains(ie, what the combination of herceptin and tykerb does) does anything to block the development compensatory upregulation of ER, IGFR or other growth factor pathways via "crosstalk"

The fact that tykerb also should block her1 and her 4 via their internal domains and the fact that her3 does not have a phosphorylation site on its own internal domain theoretically should improve the blockade, but even the house studies found it necessary to add blocking of her3 via its external domain (pertuzumab) to block gowth

If you have literature showing this is the case, please post it as it would eliminate the need for panher blockers like pertuzumab, IGFR inhibitors, etc

chrisy · 05-24-2010, 09:14 AM

Flori,
I was traveling over the weekend and unable to reply to your post (my technology failed me).

I'm with Barbara H on the side effects - as well as speaking for the efficacy of TDM1. I think she meant she started in 2007 tho, not 1997

. I started in Feb 08 and am still dealing with the same side effects - low platelets, high liver enzymes, mild flu-like symptoms a day or so post infusion. But also, still able to get treatment, yank out the IV when it's done, and go do whatever!

It might just put the lights out, so to speak, on the sternum mets. Since they are active (albeit stable) you may qualify for the study. I hope so.

True, no indication that TDM1 would be protective of the brain - except as you said to shut down anything that might feel like wandering up there. With your long Tykerb run and stable elsewhere you're starting from a good place.

You wrote the original rap on this drug, I think it is time to give it a try if you can! Knowing you can go back to what has been holding things stable is a good fall back.

Barbara H. · 05-24-2010, 01:50 PM

You are right', Chrisy. I started in 2007. Fortunately, I never had mild flu symptoms, except for the very first infusion. However, I hated getting the nosebleeds. I still think that it is a great drug.
Barbara H.

1rarebird · 05-24-2010, 02:42 PM

Lani-- You are correct about the unpublished value of blocking both ends of the Her2 receptor. I probably used an imprecise term when referring to "cross-talk" and am guilty of mixing apples with oranges. The dual blocking I was trying to discuss involves the ER and Her2+ receptors. I was trying to point out that I believe some research has been documented which shows ER+ and Her2+ breast cancers may not respond as well as hoped to either tratuzumab or anti-estrogen therapy, when they are used alone and not concurrently with the other. I came away with this understanding by reading information in web-based references such as:

http://www.medpagetoday.com/MeetingCoverage/IMPAKT/19995
http://her2support.org/vbulletin/showthread.php?t=38998
http://www.medpagetoday.com/MeetingCoverage/AACR/19632
http://clincancerres.aacrjournals.org/content/11/2/865s.abstract?ijkey=a0c53aa508e1b27bedaf4f4a7dfc44 c0acc4c701&keytype2=tf_ipsecsha

What was described in the above references sounded to my untrained ears as something akin to "cross-talk". At any rate, I believe the researchers hypothesize that using an anti-estrogen compound plus an agent to impact Her2+ receptors should yield better response to these double positive cancers. I recall that Tykerb, Herceptin and probably Neratinib could be used as the Her2 + drugs, while the SERMs and A/Is could be used as the anti-estrogen drugs.

I could have this all wrong and I hope I have not confused anyone. It was not intentional on my part. I would note that at my last meeting with my oncologist, when I brought this "cross-talk" issue up, he seemed to know what I was concerned about and promised we would discuss it in more detail when I get nearer to the end of my Herceptin-year.

As you can see from my signature, this is important stuff to me and it becomes quite complicated to me at times. Thanks for asking.--bird

runtolive · 05-25-2010, 05:48 AM

there is zero data to support that tdm1 has any effect on the brain mets, it doesnt cross the blood brain barrier.
therefore a tykerb/tdm1 would be a possible combo for multiple met sites.

jml · 05-25-2010, 08:35 AM

Flori~
Just want to send you good luck screening for the TDM1 Expanded Access trial.
I know it's hard not to consider all the possible scenarios about changing your treatment, but right now all you can do is provide them with all your records, and they'll make the decision about whether your a candidate or not.
Best case scenario is they'll say you ARE a candidate and then you have a couple of good options to choose from. But if the"stable" sternum mets prevent your from having access to the drug through this program, remember that TDM1 will be approved very soon, and very soon we'll all have the option and access to the drug.
Please keep us posted on how things go & know that we're all here rooting for you~

Jessica

SoCalGal · 05-25-2010, 05:36 PM

Here's my update from my meeting with the TDM1 expanded access clinical trial nurse & doctor:

I think what I am slowly understanding that everyone except me thinks I'm doing well. I just keep thinking I need to find something to GET RID OF (cure) these f****** sternum mets. (My oncologist gently said, I wish there was a cure, too).

TDM1 Doc explained that my lungs being pet negative is considered a total response to treatment. Sternum being "stable intensely metabolic..." means stable. Markers rolling up means I "most likely" could qualify for TDM1. Would need a 28 day wash out and re-staging, scans, blood, echo heart.

PRO's:
TDM1 MIGHT CURE ME

CONS:
1. TDM1 MIGHT "ONLY" KEEP ME STABLE
2. Insurance might not let me go back to my current regime if I progressed on TDM1.
3. BRAIN - unprotected (without Tykerb and treatment) while I do a wash-out
4. NO GUARANTEE OF ACCEPTANCE - meanwhile I'm washing out treatment
4. TRIAL LOCATION way out of my comfort zone - physically and emotionally
5. Single agent regime verses multiple blockers
6. Talk of TDM1 w/pertuzamab - might be a better option for me
7. IF I WAIT TOO LONG TO DECIDE, THERE MAY NOT BE ROOM FOR ME

THOUGHTS:
My onc says I could do my pet scan early and depending on the results it can help me decide. I'm getting my brain MRI on Sunday, so that is good in any event.

chrisy · 05-25-2010, 06:09 PM

Flori,

You've got a long list of cons there. Are you telling yourself this is not the trial for you?

As you know I'm a big fan of TDM1,and for me it has worked well as a single agent. But I'll try not to let that bias me too much.

That said, your concerns are valid - physically and emotionally out of your comfort zone is a big deal; going into a trial is a big commitment if you aren't really, well, committed.

Personally I'd love to be in a TDM1/Pertuzumab trial (I wouldn't be eligible though because of prior TDM1!). If you think that is a real possibility it might be worth holding out for that.

It seems like you really are doing quite well with your current scheme, as well as how you got there. A powerful synergy of your own wisdom and the right doors miraculously opening just when you are ready.

Go to your inside place (the wise one, not the screaming one) and listen to your heart. You will make the right choices.

Much love
Chris

SoCalGal · 05-26-2010, 09:12 AM

I had hoped to wake up with clarity...instead had a restless night so I'm just going to keep adding to this list until I know what to do.

PRO's:

TDM1 MIGHT CURE ME
TDM1 MIGHT "ONLY" KEEP ME STABLE
TDM1 - side effects could be less harsh than the Tykerb poops, and dehydration, Avastin blood pressure climb. Herceptin headaches would remain, but they are way less without Tykerb.

CONS:

TDM1 MIGHT "ONLY" KEEP ME STABLE
Insurance might not let me go back to my current regime if I progressed on TDM1.
BRAIN - question of being unprotected - side note: 2008 Brain met - grew while on Tykerb but not yet on Herceptin, Avastin, etc.
NO GUARANTEE OF ACCEPTANCE - meanwhile I'm washing out treatment, risking, etc.
TRIAL LOCATION out of my comfort zone - physically and emotionally
Single agent regime verses multiple blockers - maybe a consult w/John Glasby at UCLA again would help?
TDM1 w/pertuzamab - might be a better option for me - should be trials soon
IF I WAIT TOO LONG TO DECIDE, THERE MAY NOT BE ROOM FOR ME (feels like 20 years ago, when I was trying to get my kids into private schools, 400 hundred kids, 15 spots. We moved into a public district. ha)

THOUGHTS:

I could start Tykerb again today, and get thru another month and see what my next scan says.
I could also call the trial nurse, and ask her if she would notify me when they've filled (10) spots. Maybe buy a little time that way.
No one is saying, "Flori don't do this trial".
I think MAYBE my timing is off. I like to jump into things, right away, done deal, etc. Maybe in this setting it's better to squeak out as much time without change in regime.
Will there will be more info at ASCO that can help me decide?
LIMBO IS MY ENEMY.

Thanks for all your feedback and reflections...
Flori

hutchibk · 05-26-2010, 09:44 AM

You are doing good work, Twinkie... covering all the bases and doing all the proper analysis. I have nothing of wisdom to offer above what the much more brilliant than me, Chrisy, has offered, except this... which my onc always tells me, and I don't know if it will help at all (especially when you are struggling with everyone else thinking you are in good shape except for you...) but here goes (regarding longterm mets patients): "we are running a marathon, not a sprint."

hutchibk · 05-26-2010, 09:52 AM

(also food for thought for runtolive, etc)...

One thing my onc tells me to consider, because he has to consider it constantly, is that even though there may be no evidence that something will cross the BBB, there is also the very good potential that it does. He is not entirely convinced that the BBB is as impenetrable as is presented, because as he says, the cancer cells were able to penetrate/breach it to begin with.

Also, keep in mind the theory that after you have been on Tykerb and other BBB crossing treatments (Carbo, etc) that the BBB has been breached to a degree that might allow other treatments, that are considered larger molecule, to cross the BBB.

chrisy · 05-26-2010, 05:28 PM

Brain met grew on Tykerb, but not on herceptin. Tdm1 is herceptin.

SoCalGal · 05-28-2010, 08:55 AM

On 6/15 I'm going to have my next (determining) PET/CT scan at my own local facility. Want to compare apples to apples and not suddenly throw in a scan provided by the clinical trial doc, different pathologist, machine, language etc. Clinical trial will follow me with CT scans but will accept my 6/15 PET/CT.

That will be a 3 mo follow-up and I will base my decision on the results. If I am again stable, I will stay the course, until I am forced to change.

My question has never been TMD1 or not TDM1 - it's always been what I would reach for next. The issue is WHEN will I need it and WILL it be available.

Without question, if it was FDA approved now, I would feel no crazy pressure to make a change. The pressure I'm feeling is because a change is a-coming and WHAT IF it's not available when I need it?

I think I can wait two weeks to decide, and that if a change is needed, I will find ONE spot for me on TDM1. Meanwhile, back to Tykerb for added synergy. If I need to wash out then I will at least plan something to enjoy the break a lot more than I've enjoyed this process.

Sunday Brain MRI. Hopefully nothing bad will show up. Thank you all for your help and feedback. I think I will know what to do in two weeks. Love, love, love,
Flori

hutchibk · 05-28-2010, 10:56 AM

I am pretty much right there with you Flori... on the same path. I have new spot on my adrenal gland. A follow-up brain MRI is on June 9. I continue on Herceptin/Tykerb and we have now gone back to Tamoxifen. My old onc and my new onc BOTH want me to apply for a spot in the TDM-1 expanded access when it announces in Texas. I plan to be on the ready for that...

You have a good plan, good work Twinkie!