Does tdm1 work after herc+Tyk

[fullofbeans]

I am on herc and tyk and I had been progessing slowly accordin to scan between Jan and Jul (started tyk in Feb) (before treatment with PTACE) therefore I should be changing really..

My question is: do people that have prog on herc and tyk (I have never responded to it or maybe it slowed down the growth only) have responded to another her2 bashing agent?

Anyone have anyone been there? (starting to think what I will do next and if I should try looking into that)

[hutchibk]

I moved from Ty/Herc in March to TDM1. If you think it's the next step for you, you need to call on Monday to try and start the process.... enrollment for the compassionate use/EAP closes on Sept. 6!!

http://www.clinicaltrials.gov/ct2/show/NCT01120561?term=TDM-1&cond=breast&rcv_s=05%2F01%2F2010&rank=1

Please refer to this study by its ClinicalTrials.gov identifier: NCT01120561

Contacts
Contact: Trial Information Support Line 888-662-6728

Locations
United States, California
Investigational Site Highland, California, United States, 92346
Investigational Site Stockton, California, United States, 95204
United States, Colorado
Investigational Site Denver, Colorado, United States, 80220
United States, Florida
Investigational Site Davie, Florida, United States, 33328 United States, Illinois
Investigational Site Chicago, Illinois, United States, 60612
United States, Indiana
Investigational Site Lafayette, Indiana, United States, 47905
United States, Iowa
Investigational Site Cedar Rapids, Iowa, United States, 52403
United States, Kentucky
Investigational Site Louisville, Kentucky, United States, 40245
United States, Michigan
Investigational Site Detroit, Michigan, United States, 48201
United States, Missouri
Investigational Site St. Louis, Missouri, United States, 63141
United States, South Carolina
Investigational Site Charleston, South Carolina, United States, 29414
United States, Tennessee
Investigational Site Nashville, Tennessee, United States, 37203
United States, Texas
Investigational Site San Antonio, Texas, United States, 78229
United States, Virginia Investigational Site Fairfax, Virginia, United States, 22031

[hutchibk]

It's working very well for me so far... and I had a good 2 yr run on Ty/Herc also.

[Ellie F]

FOB
That's a really good question.
Could you try to get on the trial here? Unfortunately it's randomised so you would only have a 50% chance of getting T-DM1 but that may be worth a try as the only other option would be to go abroad for the duration of treatment. Haven't researched whether EAP is available in Europe or just the States. I hope that when it's finally approved in America that we won't encounter the problems we had with NICE and lapatinib!
Ellie

[fullofbeans]

Thanks you Ellie,

I was never re-tested for her2 and my lack of response to tyk and herc (or slow growth perhaps I do not know, it seemed that it was slowed down but who knows).

I wonder if I should do a Her2 serum to see that I am indeed def still her2 but wish I could do a P95 her2 test..

I think we are years away of it being approved because FDA has refused quick approval and therefore the review for approval is only planned for mid 2012.. then another year at the very least for the EU maybe much more.. Silly.

It seems to me that we should organise ourselves the way patient advocacy group for hiv organised themselves in the 80s and 90s to push for faster research and relaxed laws for trials. They achieved a lot I guess they were much younger and in good health unlike patients for cancer older and tired from treatments..

[Ellie F]

Hi Fob
I think you're right. With HIV they used a number of celebrities also to push the issue forward (thinking Elton John for one!). It seems we also have celebrity bc survivors and supporters but there focus seems to be fundraising (which is good i know) rather than political activism.I think the issue of older and ground down by treatments also rings true.
It is very frustrating to come to terms with the delay once drugs are approved in the States. You would think in this global economy they could synchronise approval wouldn't you! I am also concerned that as the economy remains in a poor state NICE will be in no hurry to approve expensive treatments and the investment in research may diminish.

I think your idea of checking the status of your mets is a really good idea especially in the light of what the research has showed. Would you onc go along with this? I know it was only when I had a second opinion that this happened for me as I was told it's expensive.

Ellie

[fullofbeans]

Well I cannot re-test tissues unless they do a biopsy of my lungs ( they will not do the mammary gland since apparently that is a strange/dangerous place to reach). This is why I wonder if the serum would give me some response. They tend to assume that if you were her2 you stay her2. Whereas you could have been negative before but become positive.

Does anyone knows if the Her2 serum level can be used to see whether you are her2?

Advocacy: yes it seems to me that her2 have enough bits and bobs blocking the pathway that everyone before dying should be allowed to try a number of recombination, surely. It seems we are quite close to block that pathway but are taking years to try any new combination. Expanding access prog should be the norm.

[fullofbeans]

I think I have answered my question:

http://www.ncbi.nlm.nih.gov/pubmed/17963511
Breast Cancer Res. 2007;9(5):R74.
Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status.
Fehm T, Becker S, Duerr-Stoerzer S, Sotlar K, Mueller V, Wallwiener D, Lane N, Solomayer E, Uhr J.
Source
Department of Obstetrics and Gynecology, University of Tuebingen, Calwerstrasse, D-72076 Tuebingen, Germany. Tanja.fehm@t-online.de
Abstract
INTRODUCTION:
At the time when metastatic disease is identified, assessment of human epidermal growth factor receptor (HER)2 status might help to optimize treatment decisions if HER2 status was not determined at first diagnosis and if HER2 positivity has been acquired during disease progression. Within this context, determination of serum HER2 or evaluation of HER2 status in circulating tumor cells (CTCs) may be of clinical relevance because metastatic tissue may be difficult to obtain for analysis as a result of its localization. The aim of this study was therefore to determine the HER2 status in serum and corresponding CTCs in patients with metastatic breast cancer whose primary tumors were HER2 negative or of unknown HER2 status.

METHODS:
Blood samples were obtained from 77 metastatic breast cancer patients with negative (n = 44) or unknown (n = 33) HER2 status. Serum HER2 was determined using a commercial HER2/neu ELISA kit. CTCs were detected by slide-based assay using immunomagnetic enrichment and characterized by phenotyping and genotyping. Alternatively, a commercial kit, based on RT-PCR, was used to detect and characterize CTCs.

RESULTS:
Twenty out of 77 patients with metastatic disease had elevated serum levels of HER2. Blood samples could be analyzed for the presence of CTCs in 67 patients. Eight out of 21 patients with detectable CTCs exhibited HER2 amplification. Twenty-three out of 77 patients were HER2 positive using at least one method. Concordance between HER2 status of CTCs and serum HER2 was observed in 15 of 21 patients (71%). In six patients conflicting results were obtained. Three patients with elevated serum HER2 status had HER2-negative CTCs, whereas three patients with HER2-positive CTCs had normal serum HER2 levels.

CONCLUSION:
A subgroup of patients with initially negative or unknown HER2 status can have elevated serum HER2 levels and/or HER2-positive CTCs at the time of development of metastatic disease. Although only a small num

[Sheila]

FOB
I was on Herceptin/Tykern and progressed, then eventually went on TDM-1 and progressed....seems the best bet for me is Herceptin with a chemo agent....it controls the mets for a time, then a new chemo agent needs to be added. Hope this helps...everyone is so different in response, you almost need to try each regimen and find your fit.

[hutchibk]

Sorry FOB, I forgot that you were UK, so my post about enrolling before Sept 6 in the EAP was moot...

[Julie2]

Dear FOB,

TDM1 worked for me for 6 months after I failed on Hercpetin and Tykerb.

Julie

[fullofbeans]

Thanks all

Sheila, sorry to hear that you progressed on tdm1 and by the look o it tyk/herc did not help for long at all..how are you doing on gemzar (it's gemcetabine right?) and what side effcet had you had? I am thinking low dose gem..I am thinking that perhaps people that do not respond to tyk/herc may not respond to tdm1..

Hutch, no worries about your post, it may help someone else tho

Julie, you did not fail tyk/herc they failed you! Had you responded o Tyk/herc? did it keep it in check or stable for any amount of time?

Ellie, also bc groups are focused on research as you say because they do not feel in immediate danger, unlike stage 3 & 4. hiv patient are/were all under the same amocles sword and knew that their turn would come, not simply in 20% of the case..and they do not know what we have to go through to get treatments and how humiliating it is to be ramdomised (and not be offered the drug if you prog) and excluded for this and this.

[Sheila]

FOB
I had a really good run with Eribulen (Halaven)...8 months...my Gemzar (Gemcitabine) had to be reduced....my counts were nosediving....so far, just a little nausea day 1, no hair loss, maybe some fatigue from the low counts. It seems as long as I keep Herceptin in the mix, I do OK for a while...then, the cancer gets smart, and we change the treatment. Hoping I am meant to try all the drugs!

[fullofbeans]

Sheila check that about gemzar: looks like low dose is better and obviously better tolerated that high dose.

Comparison of standard-dose and low-dose gemcitabine regimens in pancreatic adenocarcinoma patients: a prospective randomized trial.
Sakamoto H, Kitano M, Suetomi Y, Takeyama Y, Ohyanagi H, Nakai T, Yasuda C, Kudo M.
Source
Department of Gastroenterology and Hepatology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.
Abstract
BACKGROUND:
A prospective, randomized study was performed to determine whether gemcitabine infusion at a low dose (250 mg/m2) is comparable or superior to the standard-dose infusion (1000 mg/m2) in terms of the survival period, clinical benefit, and frequency of adverse effects in patients with advanced pancreatic adenocarcinoma.

METHODS:
Twenty-five patients who were histologically proven to have locally advanced pancreatic cancer or pancreatic cancer with distant metastases were initially enrolled in the present study. They were treated with gemcitabine infusion at either a dose of 1000 mg/m2 over 30 min (the standard regimen) on days 1, 8, and 15 of every 4-week cycle or at a dose of 250 mg/m2 over 30 min every week. Survival time, response rate, time to treatment failure, clinical benefit response, and adverse effects were compared between the two groups.

RESULTS:
Twenty-one patients received gemcitabine for more than 1 month. The median survival period was 7.2 months for patients who received the low-dose infusion regimen, in contrast to 5.2 months for patients administered the standard-dose infusion regimen. The time to treatment failure was 5.6 months for patients in the low-dose infusion regimen, in contrast to 3.4 months for patients in the standard-dose infusion regimen. There were no significant differences in either survival time to time to treatment failure or clinical benefits between the two groups, but the incidence of adverse reactions in patients administered the low-dose therapy was significantly lower than that in patients receiving the standard-dose therapy (P<0.05). In particular, patients in the standard infusion regimen group experienced more hematologic toxicity than those in the low-dose regimen.

CONCLUSIONS:
These findings suggest that the low-dose gemcitabine infusion regimen can be continuously administered to patients with locally advanced and systemically spreading pancreatic cancer because of its reduced toxicity, resulting in better quality of life and an improved safety profile as compared to the standard infusion treatment regimen.

[Julie2]

Tykerb and Herceptin worked for me for 9 months first time then I took Navelbine again and after the progression on Navelbine I took Herceptin and Tykerb for the second time and it kept me stabel for 6 months.

Julie

[Rich66]

Julie2's situation is a great instance of being able to gain benefit from a previously used drug. I have to say I'm surprised it worked again after only one other regimen. I've kind of assumed it would take more time to sort of come full circle. But that's great to see it's worth trying.