What can we do about the delay of TDM-1 - Page 3

schoonder · 09-06-2010, 05:33 AM

T-DM1 was developed during the days that Susan Desmond-Hellman presided over product development at Genentech, presently she's chancellor at UCSF. Her support would strengthen this case from the technical perspective. Chrisy could possibly get to see her, win her over on this subject matter when at UCSF.

hutchibk · 09-06-2010, 10:16 AM

Sounds like Chrisy is our linch-pin to a few good ideas...

And just a recap of some of the ideas:

"get ducks in a row"
1. reach out to Genentech
2. reach out to Dr. Slamon (Dr. Sledge or Dr. Julie Gralow in Seattle at SCCA, she is running a TDM1 study and could advise us.)
3. reach out to Susan Desmond-Hellman
4. reach out to Komen, (Dr. Winer is on Board of Science Advisors)

"media outreach"
1. reach out to GMA/national TV talk shows
2. reach out to local TV in cities where survivors live
3. reach out to cable news channels
4. reach out to women's magazines

"Lobbying/advocacy"
1. reach out to KOMEN for lobbying and support to cut through bureaucratic walls.
2. reach out to our local Senators and Congressfolks.
3. reach out to Lily Tartikoff.

(I am scheduled to be the subject of a monthly spotlight on breast cancer survivors on our local ABC affiliate in either Oct or Nov, will highlight the TDM-1 problem, as well as a follow-up article on me in CURE Magazine before SABCS, in which Kathy LaTour also knows I will highlight the TDM-1 refusal...)

ElaineM · 09-06-2010, 10:24 AM

Thanks for helping us stay organized Brenda. Thanks for highlighting TDM1 in your upcoming interviews.
Keeping T DM1 in the spotlight will help. If each one of us "talks it up" to our medically related contacts that will help too. Let's keep T DM1 in the spotlight whatever way we can.
"The squeaky wheel gets the oil."
Smile.

chrisy · 09-06-2010, 10:49 AM

Brenda - well organized indeed. I've spent all morning researching the discussion on other websites and sending emails.

Your earlier post on this thread, about needing to have clear, concise and scientifically factual info is critical. Talking points if you will.

I also found some good discussions on other boards so far, including this one:

http://www.inspire.com/groups/advanc...ecent-setback/

Midwest Alice · 09-06-2010, 06:29 PM

10/16/10 Metastatic Breast Cancer Network conference in Indiana
I am 3 hours away and will be going.

We should be able to launch a media campain from this conference.

I can write letters to the editor about the people I meet there and the effect the FDA rulling will have on their life. I will try the Wallstreet journal and the Indy Star.

If we could do video interviews of women who would have started theatment we could put it on youtub. I don't know how to do that. I can run a vido camera and maybe interview willing women at the conference.

My daughter is a marketing person. Maybe I can get her to go with

The November elections are not far off. Go to rallys and debates and hang around till the end and meet the people who our running for office. They need to see are faces and feel our hand in theirs. We need them to remember us and our story.

chrisy · 09-06-2010, 09:21 PM

All of these ideas are great. With Pinktober just around the corner, there should be opportunities to generate conversation. However, that is a month away... When placed in context with the FDA's pending decision on Avastin, it's clear to me that the voices of both metastatic bc patients and Her2+ patients are not being heard.

I suggest, based on some conversations I've had in the past day or so, that if we want to have impact we need to act now, while the issue is "fresh". And continue to keep the volume up after that.

The most immediate impactful action we can take is to individually, as a group, and in concert with others (the outreach to Komen and other groups with interests in common) is to write to the FDA, copy our representatives in Congress - as well as those with aspirations to become our congresspeople and senators.

Who remembers the end of Miracle on 34th street??? Our response needs & deserves the "put it here on my desk" treatment. Since we probably won't be invited, we'll have to put it there ourselves - via email, snail mail, fax. But just as many bags. Again, they need to hear our voice.

I agree with I think Brenda's comment; we must be succinct and factually accurate; but the issue is not only a scientific one, it is a perspective.

Let's hear it - what are the salient points we would need to include in such a letter? If we can design a basic format then we can pass it on and people can send, amend, personalize or whatever...

Here are a few points (NOT succinct, yet!) we might be able to use:

We are Stage IV breast cancer patients. We have benefited from TDM1 or need access to TDM1 because we are running out of options or want options that offer good QOL. Our need is now...not 3 years from now.

We are Her2+ breast cancer patients. Science is moving very fast towards targeted and personalized treatment. Her2 overexpression in BC became a prime therapeutic target, with game changing results.

We are asking the FDA to consider the unique needs of the metastatic breast cancer community, and the Her2 cancer community. (how many people IS that, anyway?)

For people living with metastatic disease, it is important to have options. (what does that mean for you?)

Options that enable us to live more fully and with greater quality of life are a big deal. Phase II studies indicate TDM1 has a low incidence of significant side effects, especially compared to traditional chemo. Although I'm just a single datapoint, I personally have enjoyed great QOL on TDM1

Time is also a big deal - what Stage IV patients need MOST is faster access to therapies that can extend life and improve quality of life. True, we don't want to sacrifice good science on the alter of expedience - but more importantly, we mustn't sacrifice LIVES on the alter of caution. Stage IV patients simply cannot wait.

Emerging science is our best hope and tailoring therapy to the individual's disease is key. Requiring patients to run the gauntlet of "one size fits all" therapies as a precondition to try the "custom made therapy" seems completely the wrong direction.

The approval process needs to keep up with the science.

What have I missed? (I deliberately left out any personal opinions and tried to be rational - after all if I'm trying to influence someone at the FDA I'd rather have the letter actually have a chance of being read!)

If you've already written, or are writing a letter could you share it here?

hutchibk · 09-06-2010, 09:41 PM

The sentence "regardless of HER2 status" disturbed me the most in the decision... ~ you can't approach efficacy of potential new treatments for HER2 cancer from a "regardless of HER2 status" standpoint... IT IS ALL ABOUT THE HER2 STATUS. That is why they are developing these targeted treatments, because if the other available treatments that "have not been exhausted by the study patient population, regardless of HER2 status" worked for us, then there would be no need for intense research and focus on treating this subgroup. By the time we exhaust those other treatments, it is often the end of our road... with progression to the point that it's potentially too late to try a 'new targeted treatment'....

It's sounding like a reversion back to that "one size fits all" mindset that is so scary in the bigger picture.

schoonder · 09-07-2010, 06:17 AM

FDA will probably say that T-DM1 from what they have heard so far is a very effective, relatively easy to tolerate drug for Her2+ mbc patients. They will also say how disappointed they were that due to incomplete patient population in trial, they had to issue that RTF letter and that they are now anxiously looking forward to day that this issue is resolved so they can begin to evaluate the data.

I agree with hutchibk, focus should be on "judgment error" by FDA to take into account, or assign sufficient value to fact that Genentech moved this drug into clinic to provide new options, where few or none remained, for "strictly" Her2+ mbc patient population.
Underlying reason for RTF issuance "regardless of HER2 status" is totally misguided, yes, IT IS ALL ABOUT THE HER2 STATUS.
This trial by design was not for every patient suffering from metastatic breast cancer, this was a "targeted" approach, new medication for a small subset of patients. Targeted therapy, a somewhat new and upcoming process, shouldn't require that FDA look at how "all" approved mbc medicines compare to candidate drug. Participants in this trial had failed pretty much all treatment options that provided them with "any" chance of relief.
In a follow up study Genentech showed that T-DM1 was most efficacious on those candidates with strongest Her2+ expression.

chrisy · 09-07-2010, 08:41 AM

Well said, Brenda and Schoonder. And on point. I know you won't mind if I plagiarize

I think the FDA is applying old rules to a new game, and it just doesn't work.

When we say it to the FDA, cc your congresspeople and your newspapers. I'm working on my letter now. Just the other day, the FDA reversed position on another drug they were about to pull, based on overwhelming response.

Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993

Commissioner Margaret Hamburg, M.D.
301-847-3531 (fax)
margaret.hamburg@fda.hhs.gov

Deputy Commissioner Joshua Sharfstein
301-796-5040
joshua.sharfstein@fda.hhs.gov

Director Dr. Janet Woodcock
Center for Drug Evaluation and Research
Building WO51
Room 6133
Mail stop HFD-001
301-847-8752 (fax)
janet.woodcock@fda.hhs.gov

Director Richard Pazdur, M.D.
Office of Oncology Drug Products
Building WO22
Room 2212
301-796-9909 (fax)
richard.pazdur@fda.hhs.gov

Contacting congress:
http://www.contactingthecongress.org/

Also of note, check out the attached link to the petition re the FDA pulling Avastin. Could be another path to make our voices heard. Some of the issues are the same and we have many people on this board benefiting from Avastin who potentially could lose this also!
http://www.thepetitionsite.com/3/sto...breast-cancer/

Jackie07 · 09-07-2010, 10:32 AM

Be sure to send a letter/e-mail to the Congressman/Senator of our own district. Remember Joe had said it one time, each of us represent one vote and that's what politicians most concerned about.

ElaineM · 09-07-2010, 10:45 AM

I am trying to figure out who I can send a letter to in congress. The person who I could have sent it to just resigned from the U. S. congress to campaign for governor of Hawaii. He is a long time friend of the Obama family and would remember President Obama's mother's fight with cancer. The other congress people from Hawaii have other major concerns they are trying to get through congress. I might have to wait until after the primary elections in Hawaii and then write to the person who has a good chance of replacing the Obama friend in congress. The Obama friend might know whoI I should write to. I will think about it.

schoonder · 09-08-2010, 01:28 PM

The FDA was fully justified in their ruling to issue a Refuse to File (RTF) letter re T-DM1. When questioned they surely will be able to identify directive(s) that support that decision. But therein lies the problem, what happens if particular directive(s) have flaws, are outdated, lack specificity, fail to take into account technological advances, or even more important, don't reflect the spirit of FDA's mandate?
Here we have an instance where FDA ruled that trial was incomplete because candidates that partook in this evaluation were not subjected to all possible metastatic breast cancer (MBC) remedies approved for this disease. Let's not deny that outcome of this scrutiny by FDA of patient population is factual; indeed not all available MBC treatment options were accounted for. However,let's look at the other side of the coin, are there mitigating reasons why Genentech decided not to include this missing collection of infrequently prescribed, low in its effectiveness, yet highly toxic medication as part of their trial? The answer of course is a resounding YES:
This trial was all about finding new options for “HER2- positive” women whose breast cancer progressed while on Herceptin or Tykerb, in third-line or greater setting, for which today there are no standard treatments or guidelines. FDA was fully aware of trial’s intent to address an unmet medical need strictly for “HER2-positive” patients, a small subset of overall MBC population. This study included patients that had failed on average seven (range of 3-13) regimens including both Herceptin and Tykerb which are known to work best in HER2-positive breast cancer. Not all regimens were accounted for, but the most predominant, most meaningful, most effective and all these therapies were no longer therapeutic.
One can only surmise that Genentech ruled in favor of the most immediate and timely considerations to bring what they observed to be an astonishingly effective, targeted drug to Her2-positive patients who were so desperately in need of new, viable treatment options. This urgency to save lives, led them to stop their time consuming, probably inconsequential and wasteful search to find further candidates that had been medicated with these for Her2-positive MBC rarely prescribed, ineffective therapies. As the Biologics License Application (BLA) Priority Review filing based on just phase II results strongly suggests, time considerations to market what promises to be a very effective drug was a strong driving force behind Genentech's motivation.
FDA’s uncompromising position to refuse to accept this filing based on a minor technicality, most likely brought on by shortcomings in their directive(s) dealing with newly “targeted” drugs like T-DM1, that are designed specifically for a small, Her2-positive overexpressing MBC patient population, is not only incomprehensible, but it is totally unacceptable. The consequence of this ruling, which appears to delay T-DM1’s approval process by at least two years, were instantaneous, the hope for a possible effective treatment option went poof, it disappeared into thin air and ultimately, it will result in premature demise for many an ill Her2-positive MBC patient.
Yes, this was such harsh and inappropriate ruling by FDA.

chrisy · 09-08-2010, 02:18 PM

Very well articulated. One factual error I think. Recheck the number of failed therapies. I think it was AVERAGE of seven with range of 3-13!

Add a call to action to reconsider the needs of the patients who tdm1 was made for and sent THAT to the FDA (All parties onn my earlier list) and their congressional counterparts

schoonder · 09-09-2010, 09:56 AM

Thanks Chrisy for pointing out that it was an AVERAGE of 7 prior treatments ranging from 3-13, subject post has been corrected.
Note of interest, compilation of T-DM1 data Genentech is looking at continuous to be promising and must have convinced them to broaden their attack on Her2-positive cancer. A new multinational trial in both adjuvant and neo-adjuvant settings is about to get underway, more details can be found in the clinicaltrials.gov registry.

Chelee · 09-13-2010, 02:14 AM

I posted to this thread & lost it. Ugh! Too late to start over now..have an early morning appt with onc/Herceptin.
But I want to keep this thread up at the top...it's such an important issue we have to stay on top of. I'm so impressed with all of you. Lots of great idea's you have all come up with.
I plan on writing my letter this wk...then figure out which places to send it too. Like Elaine asked...are we going to write up a petition for all to sign on top of these other ideas?

We need to be heard...and with what I've read here so far I think we can make it happen.

Chelee

schoonder · 09-19-2010, 09:59 AM

Quote from interesting article
"Critics say that science behind some medications has eclipsed old rules — and ethics — of testing them"

http://www.msnbc.msn.com/id/39253556...new_york_times

Trish · 09-21-2010, 07:18 PM

Thank you for all the work you are doing to get the TDM-1 decision reversed. My liver mets progressed on both Herceptin and Tykerb after initial positive responses (despite liver mets growing and sky high tumour markers I feel ridiculously healthy) so was really disappointed about the recent FDA decision. I live in Australia and Genentech won't apply to our Pharmaceutical Benefits Scheme until they get FDA approval. Hence my gratitude for the work you are doing. I am so frustrated by the one size fits all mentality. I hope Personalised Medicine is gaining ground (I see there is a big conference at Harvard Medical School on November) and just hope it can have some influence on bodies such as FDA and PBS here in Aust.
I will keep racking my brains about anything I can do from here.
I find it so sad to see the excited post from Joe about the expanded access for TDM-1. He tried so hard for us and I am ever grateful.
Trish
Trish

Chelee · 09-22-2010, 04:02 AM

Trish,
I so agree with your comments about Joe and his post. I can't help but think of him every single day! If he was here he would be ALL OVER this T-DM1 battle for us...he had the connections and would of known exactly who to talk too.. and what we all should be doing. So many of us were depending on TDM1. I just get angry when I think about how we are denied access to TDM1. It makes no sense at all to have us run through toxic chemo's before we can have a targeted therapy. Are we still going to do something about this TDM1 issue? I know it's so hard when many of us are seeing doctors, doing chemo and trying to keep up with all life hands us...but I hope some how we can make a difference for the sake of so many that need this drug now...or will in the very near future.

Schoonder,
Great link...it says it all. Thanks for sharing that.

Chelee

schoonder · 09-22-2010, 06:25 AM

To know Super-Herceptin, a very effective Her2+ MBC drug exists, but won't be made available for approx. 3 years because of some technicality that probably has no real bearing on drug's therapeutic activity, that ranks right up there with cruel and unusual punishment (Eighth Amendment to the United States Constitution) for the effected patient population.
http://thehill.com/blogs/congress-blog/healthcare/119305-a-plea-to-the-fda
http://abcnews.go.com/Site/page?id=3271346&cat=World News with Diane Sawyer
http://www.cbsnews.com/stories/1998/08/01/eveningnews/main15218.shtml
http://www.msnbc.msn.com/id/32359544/

Sheila · 09-23-2010, 05:22 AM

As far as a "campaign" slogan for us to base our voices on...I know when I tried to get TYKERB, and kept getting denied, I finally wrote my own appeal, and titled it
I AM DYING TO TRY THIS DRUG

It got their attention, unfortunately, by the time I got it, things had progressed and it didnt offer the punch we had hoped for.

They now have the TDM-1 where I go for early access....I was one of the first to be able to get it...waiting in the wings with the Metronomic chemo.

I went Tuesday for treatment, and here is what happened:
They have it where I go for treatment now in Chicago. I have been waiting, and since i now have progression in my neck nodes yet again, causing left facial numbness, thought my prayers had been answered. But, I was sent for a MUGA, and it shows 39%...spent all day yesterday at the cardiologist, echo cardiagram...will find out today...as of right now i have been taken off everything, Herceptin, chemo, etc.....maybe some fairy dust and hocus pocus will be my new treatment. Waiting to hear from the Dr today. Sometimes it seems like I just cant catch a break! I was diagnosed too early for Herceptin adjuvant, and now after 7 years of Herceptin and various chemos, the muga is too low for TDM-1...

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